Clinician Reviews

Updated August 30, 2021

The SGLT2 inhibitor empagliflozin achieved in EMPEROR-Preserved what no other agent could previously do: unequivocally cut the incidence of cardiovascular death or hospitalization in patients with heart failure and preserved ejection fraction (HFpEF).

MDedge News

Treatment with empagliflozin (Jardiance) led to a significant 21% relative reduction in the rate of cardiovascular death or hospitalization for heart failure (HHF), compared with placebo, among 5,988 randomized patients with HFpEF during a median 26 months of follow-up, proving that patients with HFpEF finally have a treatment that gives them clinically meaningful benefit, and paving the way to an abrupt change in management of these patients, experts said.

“This is the first trial to show unequivocal benefits of any drug on major heart failure outcomes in patients with HFpEF,” Stefan D. Anker, MD, PhD, declared at the virtual annual congress of the European Society of Cardiology.

The 21% relative reduction, which reflected a cut in the absolute rate of the trial’s primary composite endpoint of 3.3% compared with placebo, was driven mainly by a significant 27% relative reduction in the incidence of HHF (P < .001). Empagliflozin treatment, on top of standard therapy for patients with HFpEF, also resulted in a nonsignificant 9% relative risk reduction in the incidence of cardiovascular death, but it had no discernible impact on the rate of death from any cause, said Dr. Anker, professor of cardiology at Charité Medical University in Berlin.

Concurrently with his talk at the meeting, the results were published online in the New England Journal of Medicine.
 

Practice will change ‘quickly’

“This will definitely change our practice, and quite quickly,” said Carlos Aguiar, MD, chair of the Advanced Heart Failure and Heart Transplantation Unit at Hospital Santa Cruz in Carnaxide, Portugal, who was not involved in the study.

Transition to routine use of empagliflozin in patients with HFpEF should be swift because it has already become a mainstay of treatment for patients with heart failure with reduced ejection fraction (HFrEF) based on evidence for empagliflozin in EMPEROR-Reduced. A second sodium-glucose cotransporter 2 (SGLT2 ) inhibitor, dapagliflozin (Farxiga), is also an option for treating HFrEF based on results in the DAPA-HF trial, and the DELIVER trial, still in progress, is testing dapagliflozin as a HFpEF treatment in about 6,000 patients, with results expected in 2022.

About half of the patients in EMPEROR-Preserved had diabetes, and the treatment effects on HFpEF were similar regardless of patients’ diabetes status. Empagliflozin, like other members of the SGLT2 inhibitor class, boosts urinary excretion of glucose and received initial regulatory approval as an agent for glycemic control in patients with type 2 diabetes. Empagliflozin also has U.S.-approved marketing indications for treating patients with HFrEF whether or not they also have diabetes, and for reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease.

“We already use this drug class in cardiovascular medicine and to treat patients with type 2 diabetes, and we have been eager to find a treatment for patients with HFpEF. This is something that will be really significant,” said Dr. Aguiar.

Heart failure clinicians have “become familiar prescribing” SGLT2 inhibitors following approval of HFrEF indications for some of these agents, noted Mary Norine Walsh, MD, a heart failure specialist with Ascension Medical Group in Indianapolis. The new results “are good news because there have been so few options” for patients with HFpEF, she said in an interview.

EMPEROR-Preserved “is the first phase 3 clinical trial that exclusively enrolled patients with heart failure and an ejection fraction of more than 40% to meet its primary outcome,” and the results “represent a major win against a medical condition that had previously proven formidable,” Mark H. Drazner, MD, said in an editorial that accompanied the published results.

The trial’s findings “should contribute to a change in clinical practice given the paucity of therapeutic options available for patients with HFpEF,” wrote Dr. Drazner, a heart failure specialist who is professor and clinical chief of cardiology at UT Southwestern Medical Center in Dallas.

Theresa A, McDonagh, MD, MBChB, who chaired the panel that just released revised guidelines from the European Society of Cardiology for managing patients with heart failure, predicted that empagliflozin treatment for patients with HFpEF will soon show up in guidelines. It will likely receive a “should be considered” ranking despite being a single study because of the impressive size of the treatment effect and lack of well-supported alternative treatments, she commented as a discussant of the trial during its presentation at the congress. If the DELIVER trial with dapagliflozin shows a similar effect, the recommendation would likely become even stronger, added Dr. McDonagh, a heart failure specialist and professor of cardiology at King’s College, London.

More women enrolled than ever before

EMPEROR-Preserved enrolled adults with chronic HFpEF in New York Heart Association functional class II-IV and a left ventricular ejection fraction greater than 40% starting in 2017 at more than 600 sites in more than 20 countries worldwide including the United States. As background therapy, more than 80% of patients received treatment with either an ACE inhibitor or angiotensin receptor blocker (in some instances in the form of sacubitril/valsartan), more than 80% were on a beta-blocker, and about a third were taking a mineralocorticoid receptor antagonist, making them “very well treated HFpEF patients,” Dr. Anker said.

One of the most notable features of enrollment was that 45% of participants were women, giving this trial the highest inclusion of women compared with all prior studies in patients with HFpEF or with HFrEF, said Dr. Walsh. “HFpEF is very prevalent in woman,” she noted, and having this high participation rate of women in the study increases its relevance to these patients. “It’s important to be able to tell women that patients like you were in the study so we can more easily apply the lessons from the trial to you. That can’t be stressed enough,” she said.

The primary outcome occurred in 415 (13.8%) of the 2,997 patients in the empagliflozin group and in 511 (17.1%) of 2,991 patients who received placebo (hazard ratio, 0.79; 95% confidence interval, 0.69-0.90; P < .001).

The study showed a safety profile consistent with prior experience with empagliflozin, Dr. Anker added.

Pooling EMPEROR-Preserved with EMPEROR-Reduced

The investigators who ran EMPEROR-Preserved designed the trial to closely parallel the EMPEROR-Reduced trial in patients with HFrEF, and they included a prespecified analysis (EMPEROR-Pooled) that combined the more than 9,700 patients in the two studies. This showed a consistent and robust benefit from empagliflozin for reducing HHF across a wide spectrum of patients with heart failure, ranging from patients with left ventricular ejection fractions of less than 25% to patients with ejection fractions as high as 64%. However, the analysis also showed that patients with ejection fractions of 65% or greater received no discernible benefit from empagliflozin, Milton Packer, MD, reported in a separate talk at the congress.

MDedge News

“The findings demonstrate the benefits of empagliflozin across a broad range of patients with heart failure who have ejection fractions of less than 60%-65%,” said Dr. Packer, a researcher at Baylor University Medical Center in Dallas.

This apparent attenuation of an effect at higher ejection fractions “has been observed in other HFpEF trials, most recently in the PARAGON-HF trial” of sacubitril/valsartan (Entresto), he noted. Additional analyses led by Dr. Packer showed that in patients with ejection fractions below 65% the HHF benefit from empagliflozin consistently surpassed the benefit seen with sacubitril/valsartan in PARAGON-HF. But he recommended using both drugs in patients with HFpEF and an ejection fraction up to about 60%.

“If I had a patient with HFpEF I would use both drugs as well as beta-blockers and mineralocorticoid receptor antagonists,” he said during a press briefing.

Another finding from analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials together was that patients with reduced ejection fractions showed a significant 49% relative reduction in the incidence of serious renal outcomes, but this effect was completely blunted in EMPEROR-Preserved.

“Ejection fraction influences the effects of empagliflozin on major renal outcomes,” concluded Dr. Packer in a report on this analysis published simultaneously with the main EMPEROR-Preserved findings (N Engl J Med. 2021 Aug 27. doi: 10.1056/NEJMc2112411). “These data from the EMPEROR trials are unique. We have no comparable data” from any of the other reported studies of SGLT2 inhibitors,” he said.

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and by Eli Lilly, the two companies that jointly market empagliflozin (Jardiance). Dr. Anker has received personal fees from Boehringer Ingelheim and from several other companies, and he has received grants and personal fees from Abbott Vascular and Vifor. Dr. Packer has received consulting fees from Boehringer Ingelheim and from numerous other companies. Dr. McDonagh has has recent financial relationships with AstraZeneca, Cprpus, Novartis, Pfizer, and Vifor. Dr. Aguiar and Dr. Walsh had no disclosures.

[email protected]

Updated August 30, 2021

The SGLT2 inhibitor empagliflozin achieved in EMPEROR-Preserved what no other agent could previously do: unequivocally cut the incidence of cardiovascular death or hospitalization in patients with heart failure and preserved ejection fraction (HFpEF).

MDedge News

Treatment with empagliflozin (Jardiance) led to a significant 21% relative reduction in the rate of cardiovascular death or hospitalization for heart failure (HHF), compared with placebo, among 5,988 randomized patients with HFpEF during a median 26 months of follow-up, proving that patients with HFpEF finally have a treatment that gives them clinically meaningful benefit, and paving the way to an abrupt change in management of these patients, experts said.

“This is the first trial to show unequivocal benefits of any drug on major heart failure outcomes in patients with HFpEF,” Stefan D. Anker, MD, PhD, declared at the virtual annual congress of the European Society of Cardiology.

The 21% relative reduction, which reflected a cut in the absolute rate of the trial’s primary composite endpoint of 3.3% compared with placebo, was driven mainly by a significant 27% relative reduction in the incidence of HHF (P < .001). Empagliflozin treatment, on top of standard therapy for patients with HFpEF, also resulted in a nonsignificant 9% relative risk reduction in the incidence of cardiovascular death, but it had no discernible impact on the rate of death from any cause, said Dr. Anker, professor of cardiology at Charité Medical University in Berlin.

Concurrently with his talk at the meeting, the results were published online in the New England Journal of Medicine.
 

Practice will change ‘quickly’

“This will definitely change our practice, and quite quickly,” said Carlos Aguiar, MD, chair of the Advanced Heart Failure and Heart Transplantation Unit at Hospital Santa Cruz in Carnaxide, Portugal, who was not involved in the study.

Transition to routine use of empagliflozin in patients with HFpEF should be swift because it has already become a mainstay of treatment for patients with heart failure with reduced ejection fraction (HFrEF) based on evidence for empagliflozin in EMPEROR-Reduced. A second sodium-glucose cotransporter 2 (SGLT2 ) inhibitor, dapagliflozin (Farxiga), is also an option for treating HFrEF based on results in the DAPA-HF trial, and the DELIVER trial, still in progress, is testing dapagliflozin as a HFpEF treatment in about 6,000 patients, with results expected in 2022.

About half of the patients in EMPEROR-Preserved had diabetes, and the treatment effects on HFpEF were similar regardless of patients’ diabetes status. Empagliflozin, like other members of the SGLT2 inhibitor class, boosts urinary excretion of glucose and received initial regulatory approval as an agent for glycemic control in patients with type 2 diabetes. Empagliflozin also has U.S.-approved marketing indications for treating patients with HFrEF whether or not they also have diabetes, and for reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease.

“We already use this drug class in cardiovascular medicine and to treat patients with type 2 diabetes, and we have been eager to find a treatment for patients with HFpEF. This is something that will be really significant,” said Dr. Aguiar.

Heart failure clinicians have “become familiar prescribing” SGLT2 inhibitors following approval of HFrEF indications for some of these agents, noted Mary Norine Walsh, MD, a heart failure specialist with Ascension Medical Group in Indianapolis. The new results “are good news because there have been so few options” for patients with HFpEF, she said in an interview.

EMPEROR-Preserved “is the first phase 3 clinical trial that exclusively enrolled patients with heart failure and an ejection fraction of more than 40% to meet its primary outcome,” and the results “represent a major win against a medical condition that had previously proven formidable,” Mark H. Drazner, MD, said in an editorial that accompanied the published results.

The trial’s findings “should contribute to a change in clinical practice given the paucity of therapeutic options available for patients with HFpEF,” wrote Dr. Drazner, a heart failure specialist who is professor and clinical chief of cardiology at UT Southwestern Medical Center in Dallas.

Theresa A, McDonagh, MD, MBChB, who chaired the panel that just released revised guidelines from the European Society of Cardiology for managing patients with heart failure, predicted that empagliflozin treatment for patients with HFpEF will soon show up in guidelines. It will likely receive a “should be considered” ranking despite being a single study because of the impressive size of the treatment effect and lack of well-supported alternative treatments, she commented as a discussant of the trial during its presentation at the congress. If the DELIVER trial with dapagliflozin shows a similar effect, the recommendation would likely become even stronger, added Dr. McDonagh, a heart failure specialist and professor of cardiology at King’s College, London.

More women enrolled than ever before

EMPEROR-Preserved enrolled adults with chronic HFpEF in New York Heart Association functional class II-IV and a left ventricular ejection fraction greater than 40% starting in 2017 at more than 600 sites in more than 20 countries worldwide including the United States. As background therapy, more than 80% of patients received treatment with either an ACE inhibitor or angiotensin receptor blocker (in some instances in the form of sacubitril/valsartan), more than 80% were on a beta-blocker, and about a third were taking a mineralocorticoid receptor antagonist, making them “very well treated HFpEF patients,” Dr. Anker said.

One of the most notable features of enrollment was that 45% of participants were women, giving this trial the highest inclusion of women compared with all prior studies in patients with HFpEF or with HFrEF, said Dr. Walsh. “HFpEF is very prevalent in woman,” she noted, and having this high participation rate of women in the study increases its relevance to these patients. “It’s important to be able to tell women that patients like you were in the study so we can more easily apply the lessons from the trial to you. That can’t be stressed enough,” she said.

The primary outcome occurred in 415 (13.8%) of the 2,997 patients in the empagliflozin group and in 511 (17.1%) of 2,991 patients who received placebo (hazard ratio, 0.79; 95% confidence interval, 0.69-0.90; P < .001).

The study showed a safety profile consistent with prior experience with empagliflozin, Dr. Anker added.

Pooling EMPEROR-Preserved with EMPEROR-Reduced

The investigators who ran EMPEROR-Preserved designed the trial to closely parallel the EMPEROR-Reduced trial in patients with HFrEF, and they included a prespecified analysis (EMPEROR-Pooled) that combined the more than 9,700 patients in the two studies. This showed a consistent and robust benefit from empagliflozin for reducing HHF across a wide spectrum of patients with heart failure, ranging from patients with left ventricular ejection fractions of less than 25% to patients with ejection fractions as high as 64%. However, the analysis also showed that patients with ejection fractions of 65% or greater received no discernible benefit from empagliflozin, Milton Packer, MD, reported in a separate talk at the congress.

MDedge News

“The findings demonstrate the benefits of empagliflozin across a broad range of patients with heart failure who have ejection fractions of less than 60%-65%,” said Dr. Packer, a researcher at Baylor University Medical Center in Dallas.

This apparent attenuation of an effect at higher ejection fractions “has been observed in other HFpEF trials, most recently in the PARAGON-HF trial” of sacubitril/valsartan (Entresto), he noted. Additional analyses led by Dr. Packer showed that in patients with ejection fractions below 65% the HHF benefit from empagliflozin consistently surpassed the benefit seen with sacubitril/valsartan in PARAGON-HF. But he recommended using both drugs in patients with HFpEF and an ejection fraction up to about 60%.

“If I had a patient with HFpEF I would use both drugs as well as beta-blockers and mineralocorticoid receptor antagonists,” he said during a press briefing.

Another finding from analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials together was that patients with reduced ejection fractions showed a significant 49% relative reduction in the incidence of serious renal outcomes, but this effect was completely blunted in EMPEROR-Preserved.

“Ejection fraction influences the effects of empagliflozin on major renal outcomes,” concluded Dr. Packer in a report on this analysis published simultaneously with the main EMPEROR-Preserved findings (N Engl J Med. 2021 Aug 27. doi: 10.1056/NEJMc2112411). “These data from the EMPEROR trials are unique. We have no comparable data” from any of the other reported studies of SGLT2 inhibitors,” he said.

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and by Eli Lilly, the two companies that jointly market empagliflozin (Jardiance). Dr. Anker has received personal fees from Boehringer Ingelheim and from several other companies, and he has received grants and personal fees from Abbott Vascular and Vifor. Dr. Packer has received consulting fees from Boehringer Ingelheim and from numerous other companies. Dr. McDonagh has has recent financial relationships with AstraZeneca, Cprpus, Novartis, Pfizer, and Vifor. Dr. Aguiar and Dr. Walsh had no disclosures.

[email protected]

Updated August 30, 2021

The SGLT2 inhibitor empagliflozin achieved in EMPEROR-Preserved what no other agent could previously do: unequivocally cut the incidence of cardiovascular death or hospitalization in patients with heart failure and preserved ejection fraction (HFpEF).

MDedge News

Treatment with empagliflozin (Jardiance) led to a significant 21% relative reduction in the rate of cardiovascular death or hospitalization for heart failure (HHF), compared with placebo, among 5,988 randomized patients with HFpEF during a median 26 months of follow-up, proving that patients with HFpEF finally have a treatment that gives them clinically meaningful benefit, and paving the way to an abrupt change in management of these patients, experts said.

“This is the first trial to show unequivocal benefits of any drug on major heart failure outcomes in patients with HFpEF,” Stefan D. Anker, MD, PhD, declared at the virtual annual congress of the European Society of Cardiology.

The 21% relative reduction, which reflected a cut in the absolute rate of the trial’s primary composite endpoint of 3.3% compared with placebo, was driven mainly by a significant 27% relative reduction in the incidence of HHF (P < .001). Empagliflozin treatment, on top of standard therapy for patients with HFpEF, also resulted in a nonsignificant 9% relative risk reduction in the incidence of cardiovascular death, but it had no discernible impact on the rate of death from any cause, said Dr. Anker, professor of cardiology at Charité Medical University in Berlin.

Concurrently with his talk at the meeting, the results were published online in the New England Journal of Medicine.
 

Practice will change ‘quickly’

“This will definitely change our practice, and quite quickly,” said Carlos Aguiar, MD, chair of the Advanced Heart Failure and Heart Transplantation Unit at Hospital Santa Cruz in Carnaxide, Portugal, who was not involved in the study.

Transition to routine use of empagliflozin in patients with HFpEF should be swift because it has already become a mainstay of treatment for patients with heart failure with reduced ejection fraction (HFrEF) based on evidence for empagliflozin in EMPEROR-Reduced. A second sodium-glucose cotransporter 2 (SGLT2 ) inhibitor, dapagliflozin (Farxiga), is also an option for treating HFrEF based on results in the DAPA-HF trial, and the DELIVER trial, still in progress, is testing dapagliflozin as a HFpEF treatment in about 6,000 patients, with results expected in 2022.

About half of the patients in EMPEROR-Preserved had diabetes, and the treatment effects on HFpEF were similar regardless of patients’ diabetes status. Empagliflozin, like other members of the SGLT2 inhibitor class, boosts urinary excretion of glucose and received initial regulatory approval as an agent for glycemic control in patients with type 2 diabetes. Empagliflozin also has U.S.-approved marketing indications for treating patients with HFrEF whether or not they also have diabetes, and for reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease.

“We already use this drug class in cardiovascular medicine and to treat patients with type 2 diabetes, and we have been eager to find a treatment for patients with HFpEF. This is something that will be really significant,” said Dr. Aguiar.

Heart failure clinicians have “become familiar prescribing” SGLT2 inhibitors following approval of HFrEF indications for some of these agents, noted Mary Norine Walsh, MD, a heart failure specialist with Ascension Medical Group in Indianapolis. The new results “are good news because there have been so few options” for patients with HFpEF, she said in an interview.

EMPEROR-Preserved “is the first phase 3 clinical trial that exclusively enrolled patients with heart failure and an ejection fraction of more than 40% to meet its primary outcome,” and the results “represent a major win against a medical condition that had previously proven formidable,” Mark H. Drazner, MD, said in an editorial that accompanied the published results.

The trial’s findings “should contribute to a change in clinical practice given the paucity of therapeutic options available for patients with HFpEF,” wrote Dr. Drazner, a heart failure specialist who is professor and clinical chief of cardiology at UT Southwestern Medical Center in Dallas.

Theresa A, McDonagh, MD, MBChB, who chaired the panel that just released revised guidelines from the European Society of Cardiology for managing patients with heart failure, predicted that empagliflozin treatment for patients with HFpEF will soon show up in guidelines. It will likely receive a “should be considered” ranking despite being a single study because of the impressive size of the treatment effect and lack of well-supported alternative treatments, she commented as a discussant of the trial during its presentation at the congress. If the DELIVER trial with dapagliflozin shows a similar effect, the recommendation would likely become even stronger, added Dr. McDonagh, a heart failure specialist and professor of cardiology at King’s College, London.

More women enrolled than ever before

EMPEROR-Preserved enrolled adults with chronic HFpEF in New York Heart Association functional class II-IV and a left ventricular ejection fraction greater than 40% starting in 2017 at more than 600 sites in more than 20 countries worldwide including the United States. As background therapy, more than 80% of patients received treatment with either an ACE inhibitor or angiotensin receptor blocker (in some instances in the form of sacubitril/valsartan), more than 80% were on a beta-blocker, and about a third were taking a mineralocorticoid receptor antagonist, making them “very well treated HFpEF patients,” Dr. Anker said.

One of the most notable features of enrollment was that 45% of participants were women, giving this trial the highest inclusion of women compared with all prior studies in patients with HFpEF or with HFrEF, said Dr. Walsh. “HFpEF is very prevalent in woman,” she noted, and having this high participation rate of women in the study increases its relevance to these patients. “It’s important to be able to tell women that patients like you were in the study so we can more easily apply the lessons from the trial to you. That can’t be stressed enough,” she said.

The primary outcome occurred in 415 (13.8%) of the 2,997 patients in the empagliflozin group and in 511 (17.1%) of 2,991 patients who received placebo (hazard ratio, 0.79; 95% confidence interval, 0.69-0.90; P < .001).

The study showed a safety profile consistent with prior experience with empagliflozin, Dr. Anker added.

Pooling EMPEROR-Preserved with EMPEROR-Reduced

The investigators who ran EMPEROR-Preserved designed the trial to closely parallel the EMPEROR-Reduced trial in patients with HFrEF, and they included a prespecified analysis (EMPEROR-Pooled) that combined the more than 9,700 patients in the two studies. This showed a consistent and robust benefit from empagliflozin for reducing HHF across a wide spectrum of patients with heart failure, ranging from patients with left ventricular ejection fractions of less than 25% to patients with ejection fractions as high as 64%. However, the analysis also showed that patients with ejection fractions of 65% or greater received no discernible benefit from empagliflozin, Milton Packer, MD, reported in a separate talk at the congress.

MDedge News

“The findings demonstrate the benefits of empagliflozin across a broad range of patients with heart failure who have ejection fractions of less than 60%-65%,” said Dr. Packer, a researcher at Baylor University Medical Center in Dallas.

This apparent attenuation of an effect at higher ejection fractions “has been observed in other HFpEF trials, most recently in the PARAGON-HF trial” of sacubitril/valsartan (Entresto), he noted. Additional analyses led by Dr. Packer showed that in patients with ejection fractions below 65% the HHF benefit from empagliflozin consistently surpassed the benefit seen with sacubitril/valsartan in PARAGON-HF. But he recommended using both drugs in patients with HFpEF and an ejection fraction up to about 60%.

“If I had a patient with HFpEF I would use both drugs as well as beta-blockers and mineralocorticoid receptor antagonists,” he said during a press briefing.

Another finding from analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials together was that patients with reduced ejection fractions showed a significant 49% relative reduction in the incidence of serious renal outcomes, but this effect was completely blunted in EMPEROR-Preserved.

“Ejection fraction influences the effects of empagliflozin on major renal outcomes,” concluded Dr. Packer in a report on this analysis published simultaneously with the main EMPEROR-Preserved findings (N Engl J Med. 2021 Aug 27. doi: 10.1056/NEJMc2112411). “These data from the EMPEROR trials are unique. We have no comparable data” from any of the other reported studies of SGLT2 inhibitors,” he said.

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and by Eli Lilly, the two companies that jointly market empagliflozin (Jardiance). Dr. Anker has received personal fees from Boehringer Ingelheim and from several other companies, and he has received grants and personal fees from Abbott Vascular and Vifor. Dr. Packer has received consulting fees from Boehringer Ingelheim and from numerous other companies. Dr. McDonagh has has recent financial relationships with AstraZeneca, Cprpus, Novartis, Pfizer, and Vifor. Dr. Aguiar and Dr. Walsh had no disclosures.

[email protected]

Death from COVID-19 was not more likely among patients with inflammatory bowel disease (IBD) who had COVID-19 who developed new GI symptoms after becoming infected, according to international registry data from nearly 3,000 adults.

Although GI symptoms may arise in the general population of COVID-19 patients, data on the association between GI symptoms and COVID-19 in patients with IBD are limited, as are data on the association of GI symptoms and COVID-19 outcomes in this population, Ryan C. Ungaro, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.

In a study published in Inflammatory Bowel Diseases, the researchers identified 2,917 adults with IBD who developed COVID-19 using the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database, a global registry created to understand COVID-19 outcomes in IBD patients.

The researchers recorded all new GI symptoms experienced by the patients while they were infected with COVID-19. Overall, 764 (26.2%) experienced new GI symptoms and 2,153 did not. The most common symptom was diarrhea, reported by 80% of the patients, followed by abdominal pain in 34%. Nausea and vomiting were reported by 24% and 12%, respectively, of all patients.

The average age of the patients was 43 years for those with no new GI symptoms and 40 for those without new GI symptoms; overall, approximately half were women and approximately three-quarters were White. Overall, 50% of those with new GI symptoms were in remission, as was the case for 58.4% of those without.

IBD patients who developed new GI symptoms were significantly more likely to be women, of Asian race, older, or have at least one comorbidity.

The researchers found no difference in new GI symptoms in patients with Crohn’s disease and ulcerative colitis. “Patients on any medication – but in particular [tumor necrosis factor] antagonist monotherapy – were less likely to report new GI symptoms.” they wrote.

Although IBD patients with new GI symptoms were significantly more likely than were those without new GI symptoms to be hospitalized for COVID-19 in bivariate analyses (31.4% vs. 19.2%; P < .001), they were not more likely to need a ventilator or intensive care (5.8% vs. 4.6%; P < .18). In a multivariate analysis, IBD patients with new GI symptoms had no greater risk of death from COVID-19 than did those without new GI symptoms (adjusted odds ratio, 0.72; 95% confidence interval, 0.38-1.36).

The new-onset GI symptoms common to IBD patients with COVID-19 are not likely caused by underlying disease activity, given the number of patients in remission who reported new GI symptoms, the researchers wrote.

The study findings were limited by several factors including the retrospective design, potential reporting bias, and reliance on physician global assessment for disease assessment, the researchers noted. However, the results were strengthened by the large sample size, by the ability to assess GI symptoms before and after COVID-19, and by the evaluation of GI symptoms and COVID-19 outcomes.

“In summary, new GI symptoms are common in IBD patients with COVID-19 and are not associated with an increased risk of death due to COVID-19,” the researchers concluded. “Our findings suggest that an increase in GI symptoms in IBD patients should prompt consideration of a COVID-19 diagnosis.”
 

Data to guide clinical care

“There are several potential causes for common GI symptoms, such as diarrhea and abdominal pain, among patients with IBD,” Shirley Cohen-Mekelburg, MD, of the University of Michigan, Ann Arbor, said in an interview. “These can be the initial presentation of an IBD flare, a noninflammatory cause such as irritable bowel syndrome, small intestinal bacterial overgrowth, or an infection such as Clostridioides difficile or SARS-CoV-2. Each of these diagnoses require different treatments. An IBD flare may require escalation of immunosuppressive medications such as biologics or corticosteroids, which can cause harm in the context of an untreated infection. Therefore, any guidance that will increase health care providers’ awareness of the possible causes of similar GI symptoms is important in caring for our patients with IBD. This is especially true in context of a newer entity such as COVID-19 with which we are overall less familiar.”

Dr. Cohen-Meckelburg said the lack of association between GI symptoms and death in IBD is reassuring. “It is interesting to note that GI symptoms, and particularly new diarrhea, were very common among patients with IBD and COVID-19.

“Health care providers who treat patients with IBD should have a high-index of suspicion for SARS-CoV-2 infections when patients with IBD present with GI symptoms,” said Dr. Cohen-Meckelburg. “The data from the current study may help us to consider standard testing to rule out COVID-19 as an alternative diagnosis when considering whether to treat patients with IBD who develop new GI symptoms for an IBD flare. This would be similar to how we currently test for C. difficile and other enteric infections before treating IBD flares.

“Every study has its limitations, which need to be considered in interpreting findings,” Dr. Cohen-Meckelburg noted . “SECURE-IBD has provided great insight into COVID-19 infections among patients with IBD. However, the registry relies on individuals reporting cases, so there is the potential for underreporting, particularly with less symptomatic or subclinical cases.”

The study was supported in part by the Helmsley Charitable Trust with additional funding provided by Pfizer, Takeda, Janssen, AbbVie, Lilly, Genentech, Boehringer Ingelheim, Bristol-Myers Squibb, Celtrion, and Arenapharm. Lead author Dr. Ungaro disclosed serving as an advisory board member or consultant for AbbVie, Bristol-Myers Squibb, Janssen, Eli Lilly, Pfizer, and Takeda and research support from AbbVie, Boehringer Ingelheim, and Pfizer. Other coauthors disclosed similar relationships with other pharmaceutical companies. Dr. Cohen-Mekelburg had no financial conflicts to disclose.

Death from COVID-19 was not more likely among patients with inflammatory bowel disease (IBD) who had COVID-19 who developed new GI symptoms after becoming infected, according to international registry data from nearly 3,000 adults.

Although GI symptoms may arise in the general population of COVID-19 patients, data on the association between GI symptoms and COVID-19 in patients with IBD are limited, as are data on the association of GI symptoms and COVID-19 outcomes in this population, Ryan C. Ungaro, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.

In a study published in Inflammatory Bowel Diseases, the researchers identified 2,917 adults with IBD who developed COVID-19 using the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database, a global registry created to understand COVID-19 outcomes in IBD patients.

The researchers recorded all new GI symptoms experienced by the patients while they were infected with COVID-19. Overall, 764 (26.2%) experienced new GI symptoms and 2,153 did not. The most common symptom was diarrhea, reported by 80% of the patients, followed by abdominal pain in 34%. Nausea and vomiting were reported by 24% and 12%, respectively, of all patients.

The average age of the patients was 43 years for those with no new GI symptoms and 40 for those without new GI symptoms; overall, approximately half were women and approximately three-quarters were White. Overall, 50% of those with new GI symptoms were in remission, as was the case for 58.4% of those without.

IBD patients who developed new GI symptoms were significantly more likely to be women, of Asian race, older, or have at least one comorbidity.

The researchers found no difference in new GI symptoms in patients with Crohn’s disease and ulcerative colitis. “Patients on any medication – but in particular [tumor necrosis factor] antagonist monotherapy – were less likely to report new GI symptoms.” they wrote.

Although IBD patients with new GI symptoms were significantly more likely than were those without new GI symptoms to be hospitalized for COVID-19 in bivariate analyses (31.4% vs. 19.2%; P < .001), they were not more likely to need a ventilator or intensive care (5.8% vs. 4.6%; P < .18). In a multivariate analysis, IBD patients with new GI symptoms had no greater risk of death from COVID-19 than did those without new GI symptoms (adjusted odds ratio, 0.72; 95% confidence interval, 0.38-1.36).

The new-onset GI symptoms common to IBD patients with COVID-19 are not likely caused by underlying disease activity, given the number of patients in remission who reported new GI symptoms, the researchers wrote.

The study findings were limited by several factors including the retrospective design, potential reporting bias, and reliance on physician global assessment for disease assessment, the researchers noted. However, the results were strengthened by the large sample size, by the ability to assess GI symptoms before and after COVID-19, and by the evaluation of GI symptoms and COVID-19 outcomes.

“In summary, new GI symptoms are common in IBD patients with COVID-19 and are not associated with an increased risk of death due to COVID-19,” the researchers concluded. “Our findings suggest that an increase in GI symptoms in IBD patients should prompt consideration of a COVID-19 diagnosis.”
 

Data to guide clinical care

“There are several potential causes for common GI symptoms, such as diarrhea and abdominal pain, among patients with IBD,” Shirley Cohen-Mekelburg, MD, of the University of Michigan, Ann Arbor, said in an interview. “These can be the initial presentation of an IBD flare, a noninflammatory cause such as irritable bowel syndrome, small intestinal bacterial overgrowth, or an infection such as Clostridioides difficile or SARS-CoV-2. Each of these diagnoses require different treatments. An IBD flare may require escalation of immunosuppressive medications such as biologics or corticosteroids, which can cause harm in the context of an untreated infection. Therefore, any guidance that will increase health care providers’ awareness of the possible causes of similar GI symptoms is important in caring for our patients with IBD. This is especially true in context of a newer entity such as COVID-19 with which we are overall less familiar.”

Dr. Cohen-Meckelburg said the lack of association between GI symptoms and death in IBD is reassuring. “It is interesting to note that GI symptoms, and particularly new diarrhea, were very common among patients with IBD and COVID-19.

“Health care providers who treat patients with IBD should have a high-index of suspicion for SARS-CoV-2 infections when patients with IBD present with GI symptoms,” said Dr. Cohen-Meckelburg. “The data from the current study may help us to consider standard testing to rule out COVID-19 as an alternative diagnosis when considering whether to treat patients with IBD who develop new GI symptoms for an IBD flare. This would be similar to how we currently test for C. difficile and other enteric infections before treating IBD flares.

“Every study has its limitations, which need to be considered in interpreting findings,” Dr. Cohen-Meckelburg noted . “SECURE-IBD has provided great insight into COVID-19 infections among patients with IBD. However, the registry relies on individuals reporting cases, so there is the potential for underreporting, particularly with less symptomatic or subclinical cases.”

The study was supported in part by the Helmsley Charitable Trust with additional funding provided by Pfizer, Takeda, Janssen, AbbVie, Lilly, Genentech, Boehringer Ingelheim, Bristol-Myers Squibb, Celtrion, and Arenapharm. Lead author Dr. Ungaro disclosed serving as an advisory board member or consultant for AbbVie, Bristol-Myers Squibb, Janssen, Eli Lilly, Pfizer, and Takeda and research support from AbbVie, Boehringer Ingelheim, and Pfizer. Other coauthors disclosed similar relationships with other pharmaceutical companies. Dr. Cohen-Mekelburg had no financial conflicts to disclose.

Death from COVID-19 was not more likely among patients with inflammatory bowel disease (IBD) who had COVID-19 who developed new GI symptoms after becoming infected, according to international registry data from nearly 3,000 adults.

Although GI symptoms may arise in the general population of COVID-19 patients, data on the association between GI symptoms and COVID-19 in patients with IBD are limited, as are data on the association of GI symptoms and COVID-19 outcomes in this population, Ryan C. Ungaro, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.

In a study published in Inflammatory Bowel Diseases, the researchers identified 2,917 adults with IBD who developed COVID-19 using the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database, a global registry created to understand COVID-19 outcomes in IBD patients.

The researchers recorded all new GI symptoms experienced by the patients while they were infected with COVID-19. Overall, 764 (26.2%) experienced new GI symptoms and 2,153 did not. The most common symptom was diarrhea, reported by 80% of the patients, followed by abdominal pain in 34%. Nausea and vomiting were reported by 24% and 12%, respectively, of all patients.

The average age of the patients was 43 years for those with no new GI symptoms and 40 for those without new GI symptoms; overall, approximately half were women and approximately three-quarters were White. Overall, 50% of those with new GI symptoms were in remission, as was the case for 58.4% of those without.

IBD patients who developed new GI symptoms were significantly more likely to be women, of Asian race, older, or have at least one comorbidity.

The researchers found no difference in new GI symptoms in patients with Crohn’s disease and ulcerative colitis. “Patients on any medication – but in particular [tumor necrosis factor] antagonist monotherapy – were less likely to report new GI symptoms.” they wrote.

Although IBD patients with new GI symptoms were significantly more likely than were those without new GI symptoms to be hospitalized for COVID-19 in bivariate analyses (31.4% vs. 19.2%; P < .001), they were not more likely to need a ventilator or intensive care (5.8% vs. 4.6%; P < .18). In a multivariate analysis, IBD patients with new GI symptoms had no greater risk of death from COVID-19 than did those without new GI symptoms (adjusted odds ratio, 0.72; 95% confidence interval, 0.38-1.36).

The new-onset GI symptoms common to IBD patients with COVID-19 are not likely caused by underlying disease activity, given the number of patients in remission who reported new GI symptoms, the researchers wrote.

The study findings were limited by several factors including the retrospective design, potential reporting bias, and reliance on physician global assessment for disease assessment, the researchers noted. However, the results were strengthened by the large sample size, by the ability to assess GI symptoms before and after COVID-19, and by the evaluation of GI symptoms and COVID-19 outcomes.

“In summary, new GI symptoms are common in IBD patients with COVID-19 and are not associated with an increased risk of death due to COVID-19,” the researchers concluded. “Our findings suggest that an increase in GI symptoms in IBD patients should prompt consideration of a COVID-19 diagnosis.”
 

Data to guide clinical care

“There are several potential causes for common GI symptoms, such as diarrhea and abdominal pain, among patients with IBD,” Shirley Cohen-Mekelburg, MD, of the University of Michigan, Ann Arbor, said in an interview. “These can be the initial presentation of an IBD flare, a noninflammatory cause such as irritable bowel syndrome, small intestinal bacterial overgrowth, or an infection such as Clostridioides difficile or SARS-CoV-2. Each of these diagnoses require different treatments. An IBD flare may require escalation of immunosuppressive medications such as biologics or corticosteroids, which can cause harm in the context of an untreated infection. Therefore, any guidance that will increase health care providers’ awareness of the possible causes of similar GI symptoms is important in caring for our patients with IBD. This is especially true in context of a newer entity such as COVID-19 with which we are overall less familiar.”

Dr. Cohen-Meckelburg said the lack of association between GI symptoms and death in IBD is reassuring. “It is interesting to note that GI symptoms, and particularly new diarrhea, were very common among patients with IBD and COVID-19.

“Health care providers who treat patients with IBD should have a high-index of suspicion for SARS-CoV-2 infections when patients with IBD present with GI symptoms,” said Dr. Cohen-Meckelburg. “The data from the current study may help us to consider standard testing to rule out COVID-19 as an alternative diagnosis when considering whether to treat patients with IBD who develop new GI symptoms for an IBD flare. This would be similar to how we currently test for C. difficile and other enteric infections before treating IBD flares.

“Every study has its limitations, which need to be considered in interpreting findings,” Dr. Cohen-Meckelburg noted . “SECURE-IBD has provided great insight into COVID-19 infections among patients with IBD. However, the registry relies on individuals reporting cases, so there is the potential for underreporting, particularly with less symptomatic or subclinical cases.”

The study was supported in part by the Helmsley Charitable Trust with additional funding provided by Pfizer, Takeda, Janssen, AbbVie, Lilly, Genentech, Boehringer Ingelheim, Bristol-Myers Squibb, Celtrion, and Arenapharm. Lead author Dr. Ungaro disclosed serving as an advisory board member or consultant for AbbVie, Bristol-Myers Squibb, Janssen, Eli Lilly, Pfizer, and Takeda and research support from AbbVie, Boehringer Ingelheim, and Pfizer. Other coauthors disclosed similar relationships with other pharmaceutical companies. Dr. Cohen-Mekelburg had no financial conflicts to disclose.

Telehealth abortion may be just as safe and effective as in-person care, according to a small study published online in JAMA Network Open.

Of the 110 women from whom researchers collected remote abortion outcome data, 95% had a complete abortion without additional medical interventions, such as aspiration or surgery, and none experienced adverse events. Researchers said this efficacy rate is similar to in-person visits.

“There was no reason to expect that the medications prescribed [via telemedicine] and delivered through the mail would have different outcomes from when a patient traveled to a clinic,” study author Ushma D. Upadhyay, PhD, MPH, associate professor in the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco, said in an interview.

Medication abortion, which usually involves taking mifepristone (Mifeprex) followed by misoprostol (Cytotec) during the first 10 weeks of pregnancy, has been available in the United States since 2000. The Food and Drug Administration’s Risk Evaluation and Mitigation Strategy requires that mifepristone be dispensed in a medical office, clinic, or hospital, prohibiting dispensing from pharmacies in an effort to reduce potential risk for complications.

In April 2021, the FDA lifted the in-person dispensing requirement for mifepristone for the duration of the COVID-19 pandemic. However, Dr. Upadhyay hopes the findings of her current study will make this suspension permanent.

For the study, Dr. Upadhyay and colleagues examined the safety and efficacy of fully remote, medication abortion care. Eligibility for the medication was assessed using an online form that relies on patient history, or patients recalling their last period, to assess pregnancy duration and screen for ectopic pregnancy risks. Nurse practitioners reviewed the form and referred patients with unknown last menstrual period date or ectopic pregnancy risk factors for ultrasonography. A mail-order pharmacy delivered medications to eligible patients. The protocol involved three follow-up contacts: confirmation of medication administration, a 3-day assessment of symptoms, and a home pregnancy test after 4 weeks. Follow-up interactions were conducted by text, secure messaging, or telephone.

Researchers found that in addition to the 95% of the patients having a complete abortion without intervention, 5% (five) of patients required addition medical care to complete the abortion. Two of those patients were treated in EDs.

Gillian Burkhardt, MD, who was not involved in the study, said Dr. Upadhyay’s study proves what has been known all along, that medication is super safe and that women “can help to determine their own eligibility as well as in conjunction with the provider.”

“I hope that this will be one more study that the FDA can use when thinking about changing the risk evaluation administration strategy so that it’s removing the requirement that a person be in the dispensing medical office,” Dr. Burkhardt, assistant professor of family planning in the department of obstetrics & gynecology at the University of New Mexico Hospital, Albuquerque, said in an interview. “I hope it also makes providers feel more comfortable as well, because I think there’s some hesitancy among providers to provide abortion without doing an ultrasound or without seeing the patient typically in front of them.”

This isn’t the first study to suggest the safety of telemedicine abortion. A 2019 study published in Obstetrics & Gynecology, which analyzed records from nearly 6,000 patients receiving medication abortion either through telemedicine or in person at 26 Planned Parenthood health centers in four states found that ongoing pregnancy and aspiration procedures were less common among telemedicine patients. Another 2017 study published in BMJ found that women who used an online consultation service and self-sourced medical abortion during a 3-year period were able to successfully end their pregnancies with few adverse events.

Dr. Upadhyay said one limitation of the current study is its sample size, so more studies should be conducted to prove telemedicine abortion’s safety.

“I think that we need continued research on this model of care just so we have more multiple studies that contribute to the evidence that can convince providers as well that they don’t need a lot of tests and that they can mail,” Dr. Upadhyay said.

Neither Dr. Upadhyay nor Dr. Burkhardt reported conflicts of interests.

Telehealth abortion may be just as safe and effective as in-person care, according to a small study published online in JAMA Network Open.

Of the 110 women from whom researchers collected remote abortion outcome data, 95% had a complete abortion without additional medical interventions, such as aspiration or surgery, and none experienced adverse events. Researchers said this efficacy rate is similar to in-person visits.

“There was no reason to expect that the medications prescribed [via telemedicine] and delivered through the mail would have different outcomes from when a patient traveled to a clinic,” study author Ushma D. Upadhyay, PhD, MPH, associate professor in the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco, said in an interview.

Medication abortion, which usually involves taking mifepristone (Mifeprex) followed by misoprostol (Cytotec) during the first 10 weeks of pregnancy, has been available in the United States since 2000. The Food and Drug Administration’s Risk Evaluation and Mitigation Strategy requires that mifepristone be dispensed in a medical office, clinic, or hospital, prohibiting dispensing from pharmacies in an effort to reduce potential risk for complications.

In April 2021, the FDA lifted the in-person dispensing requirement for mifepristone for the duration of the COVID-19 pandemic. However, Dr. Upadhyay hopes the findings of her current study will make this suspension permanent.

For the study, Dr. Upadhyay and colleagues examined the safety and efficacy of fully remote, medication abortion care. Eligibility for the medication was assessed using an online form that relies on patient history, or patients recalling their last period, to assess pregnancy duration and screen for ectopic pregnancy risks. Nurse practitioners reviewed the form and referred patients with unknown last menstrual period date or ectopic pregnancy risk factors for ultrasonography. A mail-order pharmacy delivered medications to eligible patients. The protocol involved three follow-up contacts: confirmation of medication administration, a 3-day assessment of symptoms, and a home pregnancy test after 4 weeks. Follow-up interactions were conducted by text, secure messaging, or telephone.

Researchers found that in addition to the 95% of the patients having a complete abortion without intervention, 5% (five) of patients required addition medical care to complete the abortion. Two of those patients were treated in EDs.

Gillian Burkhardt, MD, who was not involved in the study, said Dr. Upadhyay’s study proves what has been known all along, that medication is super safe and that women “can help to determine their own eligibility as well as in conjunction with the provider.”

“I hope that this will be one more study that the FDA can use when thinking about changing the risk evaluation administration strategy so that it’s removing the requirement that a person be in the dispensing medical office,” Dr. Burkhardt, assistant professor of family planning in the department of obstetrics & gynecology at the University of New Mexico Hospital, Albuquerque, said in an interview. “I hope it also makes providers feel more comfortable as well, because I think there’s some hesitancy among providers to provide abortion without doing an ultrasound or without seeing the patient typically in front of them.”

This isn’t the first study to suggest the safety of telemedicine abortion. A 2019 study published in Obstetrics & Gynecology, which analyzed records from nearly 6,000 patients receiving medication abortion either through telemedicine or in person at 26 Planned Parenthood health centers in four states found that ongoing pregnancy and aspiration procedures were less common among telemedicine patients. Another 2017 study published in BMJ found that women who used an online consultation service and self-sourced medical abortion during a 3-year period were able to successfully end their pregnancies with few adverse events.

Dr. Upadhyay said one limitation of the current study is its sample size, so more studies should be conducted to prove telemedicine abortion’s safety.

“I think that we need continued research on this model of care just so we have more multiple studies that contribute to the evidence that can convince providers as well that they don’t need a lot of tests and that they can mail,” Dr. Upadhyay said.

Neither Dr. Upadhyay nor Dr. Burkhardt reported conflicts of interests.

Telehealth abortion may be just as safe and effective as in-person care, according to a small study published online in JAMA Network Open.

Of the 110 women from whom researchers collected remote abortion outcome data, 95% had a complete abortion without additional medical interventions, such as aspiration or surgery, and none experienced adverse events. Researchers said this efficacy rate is similar to in-person visits.

“There was no reason to expect that the medications prescribed [via telemedicine] and delivered through the mail would have different outcomes from when a patient traveled to a clinic,” study author Ushma D. Upadhyay, PhD, MPH, associate professor in the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco, said in an interview.

Medication abortion, which usually involves taking mifepristone (Mifeprex) followed by misoprostol (Cytotec) during the first 10 weeks of pregnancy, has been available in the United States since 2000. The Food and Drug Administration’s Risk Evaluation and Mitigation Strategy requires that mifepristone be dispensed in a medical office, clinic, or hospital, prohibiting dispensing from pharmacies in an effort to reduce potential risk for complications.

In April 2021, the FDA lifted the in-person dispensing requirement for mifepristone for the duration of the COVID-19 pandemic. However, Dr. Upadhyay hopes the findings of her current study will make this suspension permanent.

For the study, Dr. Upadhyay and colleagues examined the safety and efficacy of fully remote, medication abortion care. Eligibility for the medication was assessed using an online form that relies on patient history, or patients recalling their last period, to assess pregnancy duration and screen for ectopic pregnancy risks. Nurse practitioners reviewed the form and referred patients with unknown last menstrual period date or ectopic pregnancy risk factors for ultrasonography. A mail-order pharmacy delivered medications to eligible patients. The protocol involved three follow-up contacts: confirmation of medication administration, a 3-day assessment of symptoms, and a home pregnancy test after 4 weeks. Follow-up interactions were conducted by text, secure messaging, or telephone.

Researchers found that in addition to the 95% of the patients having a complete abortion without intervention, 5% (five) of patients required addition medical care to complete the abortion. Two of those patients were treated in EDs.

Gillian Burkhardt, MD, who was not involved in the study, said Dr. Upadhyay’s study proves what has been known all along, that medication is super safe and that women “can help to determine their own eligibility as well as in conjunction with the provider.”

“I hope that this will be one more study that the FDA can use when thinking about changing the risk evaluation administration strategy so that it’s removing the requirement that a person be in the dispensing medical office,” Dr. Burkhardt, assistant professor of family planning in the department of obstetrics & gynecology at the University of New Mexico Hospital, Albuquerque, said in an interview. “I hope it also makes providers feel more comfortable as well, because I think there’s some hesitancy among providers to provide abortion without doing an ultrasound or without seeing the patient typically in front of them.”

This isn’t the first study to suggest the safety of telemedicine abortion. A 2019 study published in Obstetrics & Gynecology, which analyzed records from nearly 6,000 patients receiving medication abortion either through telemedicine or in person at 26 Planned Parenthood health centers in four states found that ongoing pregnancy and aspiration procedures were less common among telemedicine patients. Another 2017 study published in BMJ found that women who used an online consultation service and self-sourced medical abortion during a 3-year period were able to successfully end their pregnancies with few adverse events.

Dr. Upadhyay said one limitation of the current study is its sample size, so more studies should be conducted to prove telemedicine abortion’s safety.

“I think that we need continued research on this model of care just so we have more multiple studies that contribute to the evidence that can convince providers as well that they don’t need a lot of tests and that they can mail,” Dr. Upadhyay said.

Neither Dr. Upadhyay nor Dr. Burkhardt reported conflicts of interests.

This story is a collaboration between KHN and “Science Friday.” 

Rafiah Maxie has been a licensed clinical social worker in the Chicago area for a decade. Throughout that time, she’d viewed suicide as a problem most prevalent among middle-aged white men.

Until May 27, 2020.

That day, Maxie’s 19-year-old son, Jamal Clay – who loved playing the trumpet and participating in theater, who would help her unload groceries from the car and raise funds for the March of the Dimes – killed himself in their garage.

“Now I cannot blink without seeing my son hanging,” said Maxie, who is Black.

Clay’s death, along with the suicides of more than 100 other Black residents in Illinois last year, has led locals to call for new prevention efforts focused on Black communities. In 2020, during the pandemic’s first year, suicides among White residents decreased compared with previous years, while they increased among Black residents, according to state data.

But this is not a local problem. Nor is it limited to the pandemic.

Interviews with a dozen suicide researchers, data collected from states across the country, and a review of decades of research revealed that suicide is a growing crisis for communities of color – one that plagued them well before the pandemic and has only been exacerbated since.

Overall suicide rates in the U.S. decreased in 2019 and 2020. National and local studies attribute the trend to a drop among White Americans, who make up the majority of suicide deaths. Meanwhile, rates for Black, Hispanic, and Asian Americans – though lower than those of their white peers – continued to climb in many states. (Suicide rates have been consistently high for Native Americans.)

“COVID created more transparency regarding what we already knew was happening,” said Sonyia Richardson, a licensed clinical social worker who focuses on serving people of color, and assistant professor at the University of North Carolina–Charlotte, where she researches suicide. When you put the suicide rates of all communities in one bucket, “that bucket says it’s getting better and what we’re doing is working,” she said. “But that’s not the case for communities of color.”
 

Losing generations

Although the suicide rate is highest among middle-aged White men, young people of color are emerging as particularly at risk.

Research shows Black kids younger than 13 die by suicide at nearly twice the rate of White kids and, over time, their suicide rates have grown even as rates have decreased for White children. Among teenagers and young adults, suicide deaths have increased more than 45% for Black Americans and about 40% for Asian Americans in the 7 years ending in 2019. Other concerning trends in suicide attempts date to the ’90s.

“We’re losing generations,” said Sean Joe, a national expert on Black suicide and a professor at Washington University in St. Louis. “We have to pay attention now because if you’re out of the first decade of life and think life is not worth pursuing, that’s a signal to say something is going really wrong.”

These statistics also refute traditional ideas that suicide doesn’t happen in certain ethnic or minority populations because they’re “protected” and “resilient” or the “model minority,” said Kiara Alvarez, a researcher and psychologist at Massachusetts General Hospital who focuses on suicide among Hispanic and immigrant populations.

Although these groups may have had low suicide rates historically, that’s changing, she said.

Paul Chin lost his 17-year-old brother, Chris, to suicide in 2009. A poem Chris wrote in high school about his heritage has left Chin, 8 years his senior, wondering if his brother struggled to feel accepted in the U.S., despite being born and raised in New York.

Growing up, Asian Americans weren’t represented in lessons at school or in pop culture, said Chin, now 37. Even in clinical research on suicide as well as other health topics, kids like Chris are underrepresented, with less than 1% of federal research funding focused on Asian Americans.

It wasn’t until the pandemic, and the concurrent rise in hate crimes against Asian Americans, that Chin saw national attention on the community’s mental health. He hopes the interest is not short-lived.

Suicide is the leading cause of death for Asian Americans ages 15 to 24, yet “that doesn’t get enough attention,” Chin said. “It’s important to continue to share these stories.”

Kathy Williams, who is Black, has been on a similar mission since her 15-year-old son, Torian Graves, died by suicide in 1996. People didn’t talk about suicide in the Black community then, she said. So she started raising the topic at her church in Durham, N.C., and in local schools. She wanted Black families to know the warning signs and society at large to recognize the seriousness of the problem.

The pandemic may have highlighted this, Williams said, but “it has always happened. Always.”
 

Pandemic sheds light on the triggers

Pinpointing the root causes of rising suicide within communities of color has proved difficult. How much stems from mental illness? How much from socioeconomic changes like job losses or social isolation? Now, COVID-19 may offer some clues.

Recent decades have been marked by growing economic instability, a widening racial wealth gap, and more public attention on police killings of unarmed Black and Brown people, said Michael Lindsey, executive director of the New York University McSilver Institute for Poverty Policy and Research.

With social media, youths face racism on more fronts than their parents did, said Leslie Adams, assistant professor in the department of mental health at Johns Hopkins Bloomberg School of Public Health.

Each of these factors has been shown to affect suicide risk. For example, experiencing racism and sexism together is linked to a threefold increase in suicidal thoughts for Asian American women, said Brian Keum, assistant professor at UCLA, based on preliminary research findings.

COVID-19 intensified these hardships among communities of color, with disproportionate numbers of lost loved ones, lost jobs, and lost housing. The murder of George Floyd prompted widespread racial unrest, and Asian Americans saw an increase in hate crimes.

At the same time, studies in Connecticut and Maryland found that suicide rates rose within these populations and dropped for their White counterparts.

“It’s not just a problem within the person, but societal issues that need to be addressed,” said Shari Jager-Hyman, assistant professor of psychiatry at the University of Pennsylvania.
 

Lessons from Texas

In Texas, COVID-19 hit Hispanics especially hard. As of July 2021, they accounted for 45% of all COVID-19 deaths and disproportionately lost jobs. Individuals living in the U.S. without authorization were generally not eligible for unemployment benefits or federal stimulus checks.

During this time, suicide deaths among Hispanic Texans climbed from 847 deaths in 2019 to 962 deaths in 2020, according to preliminary state data. Suicide deaths rose for Black Texans and residents classified as “other” races or ethnicities, but decreased for White Texans.

The numbers didn’t surprise Marc Mendiola. The 20-year-old grew up in a majority-Hispanic community on the south side of San Antonio. Even before the pandemic, he often heard classmates say they were suicidal. Many faced dire finances at home, sometimes living without electricity, food, or water. Those who sought mental health treatment often found services prohibitively expensive or inaccessible because they weren’t offered in Spanish.

“These are conditions the community has always been in,” Mendiola said. “But with the pandemic, it’s even worse.”

Four years ago, Mendiola and his classmates at South San High School began advocating for mental health services. In late 2019, just months before COVID-19 struck, their vision became reality. Six community agencies partnered to offer free services to students and their families across three school districts.

Richard Davidson, chief operating officer of Family Service, one of the groups in the collaborative, said the number of students discussing economic stressors has been on the rise since April 2020. More than 90% of the students who received services in the first half of 2021 were Hispanic, and nearly 10% reported thoughts of suicide or self-harm, program data show. None died by suicide.

Many students are so worried about what’s for dinner the next day that they’re not able to see a future beyond that, Davidson said. That’s when suicide can feel like a viable option.

“One of the things we do is help them see … that despite this situation now, you can create a vision for your future,” Davidson said.
 

A good future

Researchers say the promise of a good future is often overlooked in suicide prevention, perhaps because achieving it is so challenging. It requires economic and social growth and breaking systemic barriers.

Tevis Simon works to address all those fronts. As a child in West Baltimore, Simon, who is Black, faced poverty and trauma. As an adult, she attempted suicide three times. But now she shares her story with youths across the city to inspire them to overcome challenges. She also talks to politicians, law enforcement agencies, and public policy officials about their responsibilities.

“We can’t not talk about race,” said Simon, 43. “We can’t not talk about systematic oppression. We cannot not talk about these conditions that affect our mental well-being and our feeling and desire to live.”

For Jamal Clay in Illinois, the systemic barriers started early. Before his suicide last year, he had tried to harm himself when he was 12 and the victim of bullies. At that time, he was hospitalized for a few days and told to follow up with outpatient therapy, said his mother, Maxie.

But it was difficult to find therapists who accepted Medicaid, she said. When Maxie finally found one, there was a 60-day wait. Other therapists canceled appointments, she said.

“So we worked on our own,” Maxie said, relying on church and community. Her son seemed to improve. “We thought we closed that chapter in our lives.”

But when the pandemic hit, everything got worse, she said. Clay came home from college and worked at an Amazon warehouse. On drives to and from work, he was frequently pulled over by police. He stopped wearing hats so officers would consider him less intimidating, Maxie said.

“He felt uncomfortable being out in the street,” she said.

Maxie is still trying to make sense of what happened the day Clay died. But she’s found meaning in starting a nonprofit called Soul Survivors of Chicago. Through the organization, she provides education, scholarships and shoes – including Jamal’s old ones – to those impacted by violence, suicide, and trauma.

“My son won’t be able to have a first interview in [those] shoes. He won’t be able to have a nice jump shot or go to church or even meet his wife,” Maxie said.

But she hopes his shoes will carry someone else to a good future.

[Editor’s note: For the purposes of this story, “people of color” or “communities of color” refers to any racial or ethnic populations whose members do not identify as White, including those who are multiracial. Hispanics can be of any race or combination of races.]

KHN senior correspondent JoNel Aleccia contributed to this report. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

This story is a collaboration between KHN and “Science Friday.” 

Rafiah Maxie has been a licensed clinical social worker in the Chicago area for a decade. Throughout that time, she’d viewed suicide as a problem most prevalent among middle-aged white men.

Until May 27, 2020.

That day, Maxie’s 19-year-old son, Jamal Clay – who loved playing the trumpet and participating in theater, who would help her unload groceries from the car and raise funds for the March of the Dimes – killed himself in their garage.

“Now I cannot blink without seeing my son hanging,” said Maxie, who is Black.

Clay’s death, along with the suicides of more than 100 other Black residents in Illinois last year, has led locals to call for new prevention efforts focused on Black communities. In 2020, during the pandemic’s first year, suicides among White residents decreased compared with previous years, while they increased among Black residents, according to state data.

But this is not a local problem. Nor is it limited to the pandemic.

Interviews with a dozen suicide researchers, data collected from states across the country, and a review of decades of research revealed that suicide is a growing crisis for communities of color – one that plagued them well before the pandemic and has only been exacerbated since.

Overall suicide rates in the U.S. decreased in 2019 and 2020. National and local studies attribute the trend to a drop among White Americans, who make up the majority of suicide deaths. Meanwhile, rates for Black, Hispanic, and Asian Americans – though lower than those of their white peers – continued to climb in many states. (Suicide rates have been consistently high for Native Americans.)

“COVID created more transparency regarding what we already knew was happening,” said Sonyia Richardson, a licensed clinical social worker who focuses on serving people of color, and assistant professor at the University of North Carolina–Charlotte, where she researches suicide. When you put the suicide rates of all communities in one bucket, “that bucket says it’s getting better and what we’re doing is working,” she said. “But that’s not the case for communities of color.”
 

Losing generations

Although the suicide rate is highest among middle-aged White men, young people of color are emerging as particularly at risk.

Research shows Black kids younger than 13 die by suicide at nearly twice the rate of White kids and, over time, their suicide rates have grown even as rates have decreased for White children. Among teenagers and young adults, suicide deaths have increased more than 45% for Black Americans and about 40% for Asian Americans in the 7 years ending in 2019. Other concerning trends in suicide attempts date to the ’90s.

“We’re losing generations,” said Sean Joe, a national expert on Black suicide and a professor at Washington University in St. Louis. “We have to pay attention now because if you’re out of the first decade of life and think life is not worth pursuing, that’s a signal to say something is going really wrong.”

These statistics also refute traditional ideas that suicide doesn’t happen in certain ethnic or minority populations because they’re “protected” and “resilient” or the “model minority,” said Kiara Alvarez, a researcher and psychologist at Massachusetts General Hospital who focuses on suicide among Hispanic and immigrant populations.

Although these groups may have had low suicide rates historically, that’s changing, she said.

Paul Chin lost his 17-year-old brother, Chris, to suicide in 2009. A poem Chris wrote in high school about his heritage has left Chin, 8 years his senior, wondering if his brother struggled to feel accepted in the U.S., despite being born and raised in New York.

Growing up, Asian Americans weren’t represented in lessons at school or in pop culture, said Chin, now 37. Even in clinical research on suicide as well as other health topics, kids like Chris are underrepresented, with less than 1% of federal research funding focused on Asian Americans.

It wasn’t until the pandemic, and the concurrent rise in hate crimes against Asian Americans, that Chin saw national attention on the community’s mental health. He hopes the interest is not short-lived.

Suicide is the leading cause of death for Asian Americans ages 15 to 24, yet “that doesn’t get enough attention,” Chin said. “It’s important to continue to share these stories.”

Kathy Williams, who is Black, has been on a similar mission since her 15-year-old son, Torian Graves, died by suicide in 1996. People didn’t talk about suicide in the Black community then, she said. So she started raising the topic at her church in Durham, N.C., and in local schools. She wanted Black families to know the warning signs and society at large to recognize the seriousness of the problem.

The pandemic may have highlighted this, Williams said, but “it has always happened. Always.”
 

Pandemic sheds light on the triggers

Pinpointing the root causes of rising suicide within communities of color has proved difficult. How much stems from mental illness? How much from socioeconomic changes like job losses or social isolation? Now, COVID-19 may offer some clues.

Recent decades have been marked by growing economic instability, a widening racial wealth gap, and more public attention on police killings of unarmed Black and Brown people, said Michael Lindsey, executive director of the New York University McSilver Institute for Poverty Policy and Research.

With social media, youths face racism on more fronts than their parents did, said Leslie Adams, assistant professor in the department of mental health at Johns Hopkins Bloomberg School of Public Health.

Each of these factors has been shown to affect suicide risk. For example, experiencing racism and sexism together is linked to a threefold increase in suicidal thoughts for Asian American women, said Brian Keum, assistant professor at UCLA, based on preliminary research findings.

COVID-19 intensified these hardships among communities of color, with disproportionate numbers of lost loved ones, lost jobs, and lost housing. The murder of George Floyd prompted widespread racial unrest, and Asian Americans saw an increase in hate crimes.

At the same time, studies in Connecticut and Maryland found that suicide rates rose within these populations and dropped for their White counterparts.

“It’s not just a problem within the person, but societal issues that need to be addressed,” said Shari Jager-Hyman, assistant professor of psychiatry at the University of Pennsylvania.
 

Lessons from Texas

In Texas, COVID-19 hit Hispanics especially hard. As of July 2021, they accounted for 45% of all COVID-19 deaths and disproportionately lost jobs. Individuals living in the U.S. without authorization were generally not eligible for unemployment benefits or federal stimulus checks.

During this time, suicide deaths among Hispanic Texans climbed from 847 deaths in 2019 to 962 deaths in 2020, according to preliminary state data. Suicide deaths rose for Black Texans and residents classified as “other” races or ethnicities, but decreased for White Texans.

The numbers didn’t surprise Marc Mendiola. The 20-year-old grew up in a majority-Hispanic community on the south side of San Antonio. Even before the pandemic, he often heard classmates say they were suicidal. Many faced dire finances at home, sometimes living without electricity, food, or water. Those who sought mental health treatment often found services prohibitively expensive or inaccessible because they weren’t offered in Spanish.

“These are conditions the community has always been in,” Mendiola said. “But with the pandemic, it’s even worse.”

Four years ago, Mendiola and his classmates at South San High School began advocating for mental health services. In late 2019, just months before COVID-19 struck, their vision became reality. Six community agencies partnered to offer free services to students and their families across three school districts.

Richard Davidson, chief operating officer of Family Service, one of the groups in the collaborative, said the number of students discussing economic stressors has been on the rise since April 2020. More than 90% of the students who received services in the first half of 2021 were Hispanic, and nearly 10% reported thoughts of suicide or self-harm, program data show. None died by suicide.

Many students are so worried about what’s for dinner the next day that they’re not able to see a future beyond that, Davidson said. That’s when suicide can feel like a viable option.

“One of the things we do is help them see … that despite this situation now, you can create a vision for your future,” Davidson said.
 

A good future

Researchers say the promise of a good future is often overlooked in suicide prevention, perhaps because achieving it is so challenging. It requires economic and social growth and breaking systemic barriers.

Tevis Simon works to address all those fronts. As a child in West Baltimore, Simon, who is Black, faced poverty and trauma. As an adult, she attempted suicide three times. But now she shares her story with youths across the city to inspire them to overcome challenges. She also talks to politicians, law enforcement agencies, and public policy officials about their responsibilities.

“We can’t not talk about race,” said Simon, 43. “We can’t not talk about systematic oppression. We cannot not talk about these conditions that affect our mental well-being and our feeling and desire to live.”

For Jamal Clay in Illinois, the systemic barriers started early. Before his suicide last year, he had tried to harm himself when he was 12 and the victim of bullies. At that time, he was hospitalized for a few days and told to follow up with outpatient therapy, said his mother, Maxie.

But it was difficult to find therapists who accepted Medicaid, she said. When Maxie finally found one, there was a 60-day wait. Other therapists canceled appointments, she said.

“So we worked on our own,” Maxie said, relying on church and community. Her son seemed to improve. “We thought we closed that chapter in our lives.”

But when the pandemic hit, everything got worse, she said. Clay came home from college and worked at an Amazon warehouse. On drives to and from work, he was frequently pulled over by police. He stopped wearing hats so officers would consider him less intimidating, Maxie said.

“He felt uncomfortable being out in the street,” she said.

Maxie is still trying to make sense of what happened the day Clay died. But she’s found meaning in starting a nonprofit called Soul Survivors of Chicago. Through the organization, she provides education, scholarships and shoes – including Jamal’s old ones – to those impacted by violence, suicide, and trauma.

“My son won’t be able to have a first interview in [those] shoes. He won’t be able to have a nice jump shot or go to church or even meet his wife,” Maxie said.

But she hopes his shoes will carry someone else to a good future.

[Editor’s note: For the purposes of this story, “people of color” or “communities of color” refers to any racial or ethnic populations whose members do not identify as White, including those who are multiracial. Hispanics can be of any race or combination of races.]

KHN senior correspondent JoNel Aleccia contributed to this report. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

This story is a collaboration between KHN and “Science Friday.” 

Rafiah Maxie has been a licensed clinical social worker in the Chicago area for a decade. Throughout that time, she’d viewed suicide as a problem most prevalent among middle-aged white men.

Until May 27, 2020.

That day, Maxie’s 19-year-old son, Jamal Clay – who loved playing the trumpet and participating in theater, who would help her unload groceries from the car and raise funds for the March of the Dimes – killed himself in their garage.

“Now I cannot blink without seeing my son hanging,” said Maxie, who is Black.

Clay’s death, along with the suicides of more than 100 other Black residents in Illinois last year, has led locals to call for new prevention efforts focused on Black communities. In 2020, during the pandemic’s first year, suicides among White residents decreased compared with previous years, while they increased among Black residents, according to state data.

But this is not a local problem. Nor is it limited to the pandemic.

Interviews with a dozen suicide researchers, data collected from states across the country, and a review of decades of research revealed that suicide is a growing crisis for communities of color – one that plagued them well before the pandemic and has only been exacerbated since.

Overall suicide rates in the U.S. decreased in 2019 and 2020. National and local studies attribute the trend to a drop among White Americans, who make up the majority of suicide deaths. Meanwhile, rates for Black, Hispanic, and Asian Americans – though lower than those of their white peers – continued to climb in many states. (Suicide rates have been consistently high for Native Americans.)

“COVID created more transparency regarding what we already knew was happening,” said Sonyia Richardson, a licensed clinical social worker who focuses on serving people of color, and assistant professor at the University of North Carolina–Charlotte, where she researches suicide. When you put the suicide rates of all communities in one bucket, “that bucket says it’s getting better and what we’re doing is working,” she said. “But that’s not the case for communities of color.”
 

Losing generations

Although the suicide rate is highest among middle-aged White men, young people of color are emerging as particularly at risk.

Research shows Black kids younger than 13 die by suicide at nearly twice the rate of White kids and, over time, their suicide rates have grown even as rates have decreased for White children. Among teenagers and young adults, suicide deaths have increased more than 45% for Black Americans and about 40% for Asian Americans in the 7 years ending in 2019. Other concerning trends in suicide attempts date to the ’90s.

“We’re losing generations,” said Sean Joe, a national expert on Black suicide and a professor at Washington University in St. Louis. “We have to pay attention now because if you’re out of the first decade of life and think life is not worth pursuing, that’s a signal to say something is going really wrong.”

These statistics also refute traditional ideas that suicide doesn’t happen in certain ethnic or minority populations because they’re “protected” and “resilient” or the “model minority,” said Kiara Alvarez, a researcher and psychologist at Massachusetts General Hospital who focuses on suicide among Hispanic and immigrant populations.

Although these groups may have had low suicide rates historically, that’s changing, she said.

Paul Chin lost his 17-year-old brother, Chris, to suicide in 2009. A poem Chris wrote in high school about his heritage has left Chin, 8 years his senior, wondering if his brother struggled to feel accepted in the U.S., despite being born and raised in New York.

Growing up, Asian Americans weren’t represented in lessons at school or in pop culture, said Chin, now 37. Even in clinical research on suicide as well as other health topics, kids like Chris are underrepresented, with less than 1% of federal research funding focused on Asian Americans.

It wasn’t until the pandemic, and the concurrent rise in hate crimes against Asian Americans, that Chin saw national attention on the community’s mental health. He hopes the interest is not short-lived.

Suicide is the leading cause of death for Asian Americans ages 15 to 24, yet “that doesn’t get enough attention,” Chin said. “It’s important to continue to share these stories.”

Kathy Williams, who is Black, has been on a similar mission since her 15-year-old son, Torian Graves, died by suicide in 1996. People didn’t talk about suicide in the Black community then, she said. So she started raising the topic at her church in Durham, N.C., and in local schools. She wanted Black families to know the warning signs and society at large to recognize the seriousness of the problem.

The pandemic may have highlighted this, Williams said, but “it has always happened. Always.”
 

Pandemic sheds light on the triggers

Pinpointing the root causes of rising suicide within communities of color has proved difficult. How much stems from mental illness? How much from socioeconomic changes like job losses or social isolation? Now, COVID-19 may offer some clues.

Recent decades have been marked by growing economic instability, a widening racial wealth gap, and more public attention on police killings of unarmed Black and Brown people, said Michael Lindsey, executive director of the New York University McSilver Institute for Poverty Policy and Research.

With social media, youths face racism on more fronts than their parents did, said Leslie Adams, assistant professor in the department of mental health at Johns Hopkins Bloomberg School of Public Health.

Each of these factors has been shown to affect suicide risk. For example, experiencing racism and sexism together is linked to a threefold increase in suicidal thoughts for Asian American women, said Brian Keum, assistant professor at UCLA, based on preliminary research findings.

COVID-19 intensified these hardships among communities of color, with disproportionate numbers of lost loved ones, lost jobs, and lost housing. The murder of George Floyd prompted widespread racial unrest, and Asian Americans saw an increase in hate crimes.

At the same time, studies in Connecticut and Maryland found that suicide rates rose within these populations and dropped for their White counterparts.

“It’s not just a problem within the person, but societal issues that need to be addressed,” said Shari Jager-Hyman, assistant professor of psychiatry at the University of Pennsylvania.
 

Lessons from Texas

In Texas, COVID-19 hit Hispanics especially hard. As of July 2021, they accounted for 45% of all COVID-19 deaths and disproportionately lost jobs. Individuals living in the U.S. without authorization were generally not eligible for unemployment benefits or federal stimulus checks.

During this time, suicide deaths among Hispanic Texans climbed from 847 deaths in 2019 to 962 deaths in 2020, according to preliminary state data. Suicide deaths rose for Black Texans and residents classified as “other” races or ethnicities, but decreased for White Texans.

The numbers didn’t surprise Marc Mendiola. The 20-year-old grew up in a majority-Hispanic community on the south side of San Antonio. Even before the pandemic, he often heard classmates say they were suicidal. Many faced dire finances at home, sometimes living without electricity, food, or water. Those who sought mental health treatment often found services prohibitively expensive or inaccessible because they weren’t offered in Spanish.

“These are conditions the community has always been in,” Mendiola said. “But with the pandemic, it’s even worse.”

Four years ago, Mendiola and his classmates at South San High School began advocating for mental health services. In late 2019, just months before COVID-19 struck, their vision became reality. Six community agencies partnered to offer free services to students and their families across three school districts.

Richard Davidson, chief operating officer of Family Service, one of the groups in the collaborative, said the number of students discussing economic stressors has been on the rise since April 2020. More than 90% of the students who received services in the first half of 2021 were Hispanic, and nearly 10% reported thoughts of suicide or self-harm, program data show. None died by suicide.

Many students are so worried about what’s for dinner the next day that they’re not able to see a future beyond that, Davidson said. That’s when suicide can feel like a viable option.

“One of the things we do is help them see … that despite this situation now, you can create a vision for your future,” Davidson said.
 

A good future

Researchers say the promise of a good future is often overlooked in suicide prevention, perhaps because achieving it is so challenging. It requires economic and social growth and breaking systemic barriers.

Tevis Simon works to address all those fronts. As a child in West Baltimore, Simon, who is Black, faced poverty and trauma. As an adult, she attempted suicide three times. But now she shares her story with youths across the city to inspire them to overcome challenges. She also talks to politicians, law enforcement agencies, and public policy officials about their responsibilities.

“We can’t not talk about race,” said Simon, 43. “We can’t not talk about systematic oppression. We cannot not talk about these conditions that affect our mental well-being and our feeling and desire to live.”

For Jamal Clay in Illinois, the systemic barriers started early. Before his suicide last year, he had tried to harm himself when he was 12 and the victim of bullies. At that time, he was hospitalized for a few days and told to follow up with outpatient therapy, said his mother, Maxie.

But it was difficult to find therapists who accepted Medicaid, she said. When Maxie finally found one, there was a 60-day wait. Other therapists canceled appointments, she said.

“So we worked on our own,” Maxie said, relying on church and community. Her son seemed to improve. “We thought we closed that chapter in our lives.”

But when the pandemic hit, everything got worse, she said. Clay came home from college and worked at an Amazon warehouse. On drives to and from work, he was frequently pulled over by police. He stopped wearing hats so officers would consider him less intimidating, Maxie said.

“He felt uncomfortable being out in the street,” she said.

Maxie is still trying to make sense of what happened the day Clay died. But she’s found meaning in starting a nonprofit called Soul Survivors of Chicago. Through the organization, she provides education, scholarships and shoes – including Jamal’s old ones – to those impacted by violence, suicide, and trauma.

“My son won’t be able to have a first interview in [those] shoes. He won’t be able to have a nice jump shot or go to church or even meet his wife,” Maxie said.

But she hopes his shoes will carry someone else to a good future.

[Editor’s note: For the purposes of this story, “people of color” or “communities of color” refers to any racial or ethnic populations whose members do not identify as White, including those who are multiracial. Hispanics can be of any race or combination of races.]

KHN senior correspondent JoNel Aleccia contributed to this report. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The Food and Drug Administration has approved difelikefalin for treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis, the first agent approved from a novel class of kappa opioid receptor agonists.

Olivier Le Moal/Getty Images

Some nephrologists welcomed the Aug. 23 approval of this new option for treating pruritus, a relatively common and often hard-to-resolve complication of dialysis in patients with chronic kidney disease (CKD) that can substantially impinge on quality of life for some patients, but also voiced uncertainty about the role of a new agent with a modest trial track record that may be expensive and face insurance-coverage hurdles.

“Uptake of difelikefalin will depend on awareness of itch among patients dependent on hemodialysis, and on payment policies,” predicted Daniel E. Weiner, MD, a nephrologist at Tufts Medical Center in Boston. “Pruritus is underdiagnosed among people with kidney failure, and in some patients ongoing pruritus can be highly impactful on sleep and quality of life. The clinical trial results were very encouraging that difelikefalin is effective and safe,” which makes recognition of pruritus as a significant issue for patients a key factor in uptake of the new drug, Dr. Weiner, an investigator in a difelikefalin clinical study, said in an interview.

Other nephrologists acknowledged the substantial problem that itch can pose for many patients with CKD on dialysis but questioned the weight of evidence behind difelikefalin’s approval.
 

Two pivotal trials with fewer than 900 total randomized patients

The data considered by the FDA primarily featured results from two pivotal trials, KALM-1 and KALM-2. KALM-1 randomized 378 patients with CKD and on hemodialysis and with moderate to severe pruritus to intravenous treatment with difelikefalin or placebo three times a week for 12 weeks with a primary endpoint of an improvement (decrease) of at least 3 points from baseline in their Worst Itching Intensity Numerical Rating Scale (WI-NRS) score, which averaged just over 7 points at baseline. After 12 weeks on treatment, 52% of patients who received difelikefalin had at least a 3-point drop, compared with 31% of patients who received placebo, a significant difference. The results appeared in a 2020 report in the New England Journal of Medicine.

Confirmatory results came in the second pivotal trial, KALM-2, a similarly designed, 12-week study that randomized 473 patients, with 54% of those in the active arm achieving at least a 3-point cut in their baseline WI-NRS score, compared with 42% of patients who received placebo, a significant difference. A report at the Kidney Week meeting sponsored by the National Kidney Foundation in October 2020 presented the KALM-2 results, but the findings have not yet appeared in a published article.

In sum, the data suggest that treatment with difelikefalin will, on average, produce a clinically meaningful effect on itch compared with placebo in about 20% of patients, with nearly half the patients who receive the active drug having a less robust response and many patients who receive no active treatment also show a meaningful cut in their pruritus severity in a trial setting, noted Paul Palevsky, MD, professor of medicine at the University of Pittsburgh and chief of the renal section at the Veterans Affairs Pittsburgh Healthcare System.

The upshot is that questions linger over which patients are the best candidates for this drug and how it might perform in real-world practice given difelikefalin’s limited track record, Dr. Palevsky said in an interview.

In addition, the labeling specifies the indication is for patients with moderate to severe pruritus, but itching severity is not routinely quantified in these patients in current practice, added Dr. Palevsky, who is also president of the National Kidney Foundation.

Dr. Weiner noted that another unknown is the appropriate duration of treatment in real-world use.
 

What will it cost, and will it be covered?

The drug’s price and insurance coverage will likely be a major factor in uptake of the new drug, agreed both Dr. Weiner and Dr. Palevsky, especially the coverage decision for Medicare patients by the Centers for Medicare & Medicaid Services. A corollary is whether or not coverage for difelikefalin, which patients receive as an intravenous infusion during each of their usual three-times-a-week dialysis sessions, will lie outside of the bundled dialysis reimbursement payment. If is no mechanism exists to pay for difelikefalin separately beyond the current bundled dialysis rate, “I suspect it will not get used very much unless it is very inexpensive,” predicted Dr. Weiner.

Another issue is where difelikefalin fits within the lineup of standard treatment options. “A lot of people receiving hemodialysis suffer from pruritus and have not been successfully treated. For these individuals difelikefalin could be a game changer,” Dr. Weiner said.

Other nephrologists have a more positive take on the existing treatment options.

“Start systemic therapy for patients with itch that is significantly affecting quality of life; stepping up from topical therapy just delays effective treatment,” advised Hugh C. Rayner, MD, a nephrologist affiliated with Birmingham (England) Heartland’s Hospital who was lead author on a review of pruritus treatments for patients with CKD on hemodialysis.

“Standard systemic therapy is gabapentin or pregabalin,” an approach “supported by robust evidence confirmed in a Cochrane review,” he said in an interview. The impact of difelikefalin “will be limited as its effectiveness in reducing itch is modest at best and far inferior to gabapentin and pregabalin,” Dr. Rayner added. Difelikefalin’s “main downsides will be its cost, compared with gabapentin, and its gastrointestinal side effects.”
 

Adverse-event profiles

In KALM-1, the most frequent adverse effects from difelikefalin treatment was diarrhea, in 10% of patients, compared with a 4% rate among patients who received placebo. Vomiting occurred at a 5% incidence on difelikefalin and in 3% of patients on placebo. All serious adverse events occurred in 26% of patients on difelikefalin and in 22% of those who received placebo. Discontinuations because of an adverse event occurred in 8% of patients on difelikefalin and in 5% of the placebo patients.

An editorial that accompanied the published KALM-1 report in 2020 said “the findings are compelling, although diarrhea, dizziness, and vomiting were frequent side effects.”

Both Dr. Weiner and Dr. Palevsky were more reserved than Dr. Rayner in their appraisal of gabapentin and pregabalin, although Dr. Palevsky admitted that he has prescribed one or the other of these two drugs to “lots of patients,” especially gabapentin. “But they are not completely benign drugs,” he cautioned, a concern echoed by Dr. Weiner.

“Antihistamines, gabapentin, and pregabalin have a high side-effect burden in patients on hemodialysis and limited efficacy, and are poor options for chronic pruritus management,” explained Dr. Weiner. “I would favor difelikefalin to chronic prescription of these other agents” because difelikefalin “appears effective and has a very low side effect burden. Very few effective treatments for pruritus do not have side effects.”

Difelikefalin is a peripherally restricted, selective kappa opioid receptor agonist that exerts antipruritic effects by activating kappa opioid receptors on peripheral neurons and immune cells. The drug’s hydrophilic, small-peptide structure restricts passive diffusion across membranes, which limits the drug’s access to kappa opioid receptors in the central nervous system and hence reduces potential adverse effects.

The FDA made this approval decision without consulting an advisory committee. The companies that will market difelikefalin (Korsuva), Cara Therapeutics and Vifor Pharma, announced that their U.S. promotional launch of the drug starts early in 2022.

The KALM-1 and KALM-2 studies were sponsored by Cara Therapeutics and Vifor Pharma, the two companies that have been jointly developing difelikefalin. Dr. Pavelsky and Dr. Rayner had no relevant disclosures. Dr. Weiner was previously an adviser to Cara and Vifor and participated as an investigator in a difelikefalin clinical study, but more recently has had no relationships with the companies.

[email protected]

The Food and Drug Administration has approved difelikefalin for treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis, the first agent approved from a novel class of kappa opioid receptor agonists.

Olivier Le Moal/Getty Images

Some nephrologists welcomed the Aug. 23 approval of this new option for treating pruritus, a relatively common and often hard-to-resolve complication of dialysis in patients with chronic kidney disease (CKD) that can substantially impinge on quality of life for some patients, but also voiced uncertainty about the role of a new agent with a modest trial track record that may be expensive and face insurance-coverage hurdles.

“Uptake of difelikefalin will depend on awareness of itch among patients dependent on hemodialysis, and on payment policies,” predicted Daniel E. Weiner, MD, a nephrologist at Tufts Medical Center in Boston. “Pruritus is underdiagnosed among people with kidney failure, and in some patients ongoing pruritus can be highly impactful on sleep and quality of life. The clinical trial results were very encouraging that difelikefalin is effective and safe,” which makes recognition of pruritus as a significant issue for patients a key factor in uptake of the new drug, Dr. Weiner, an investigator in a difelikefalin clinical study, said in an interview.

Other nephrologists acknowledged the substantial problem that itch can pose for many patients with CKD on dialysis but questioned the weight of evidence behind difelikefalin’s approval.
 

Two pivotal trials with fewer than 900 total randomized patients

The data considered by the FDA primarily featured results from two pivotal trials, KALM-1 and KALM-2. KALM-1 randomized 378 patients with CKD and on hemodialysis and with moderate to severe pruritus to intravenous treatment with difelikefalin or placebo three times a week for 12 weeks with a primary endpoint of an improvement (decrease) of at least 3 points from baseline in their Worst Itching Intensity Numerical Rating Scale (WI-NRS) score, which averaged just over 7 points at baseline. After 12 weeks on treatment, 52% of patients who received difelikefalin had at least a 3-point drop, compared with 31% of patients who received placebo, a significant difference. The results appeared in a 2020 report in the New England Journal of Medicine.

Confirmatory results came in the second pivotal trial, KALM-2, a similarly designed, 12-week study that randomized 473 patients, with 54% of those in the active arm achieving at least a 3-point cut in their baseline WI-NRS score, compared with 42% of patients who received placebo, a significant difference. A report at the Kidney Week meeting sponsored by the National Kidney Foundation in October 2020 presented the KALM-2 results, but the findings have not yet appeared in a published article.

In sum, the data suggest that treatment with difelikefalin will, on average, produce a clinically meaningful effect on itch compared with placebo in about 20% of patients, with nearly half the patients who receive the active drug having a less robust response and many patients who receive no active treatment also show a meaningful cut in their pruritus severity in a trial setting, noted Paul Palevsky, MD, professor of medicine at the University of Pittsburgh and chief of the renal section at the Veterans Affairs Pittsburgh Healthcare System.

The upshot is that questions linger over which patients are the best candidates for this drug and how it might perform in real-world practice given difelikefalin’s limited track record, Dr. Palevsky said in an interview.

In addition, the labeling specifies the indication is for patients with moderate to severe pruritus, but itching severity is not routinely quantified in these patients in current practice, added Dr. Palevsky, who is also president of the National Kidney Foundation.

Dr. Weiner noted that another unknown is the appropriate duration of treatment in real-world use.
 

What will it cost, and will it be covered?

The drug’s price and insurance coverage will likely be a major factor in uptake of the new drug, agreed both Dr. Weiner and Dr. Palevsky, especially the coverage decision for Medicare patients by the Centers for Medicare & Medicaid Services. A corollary is whether or not coverage for difelikefalin, which patients receive as an intravenous infusion during each of their usual three-times-a-week dialysis sessions, will lie outside of the bundled dialysis reimbursement payment. If is no mechanism exists to pay for difelikefalin separately beyond the current bundled dialysis rate, “I suspect it will not get used very much unless it is very inexpensive,” predicted Dr. Weiner.

Another issue is where difelikefalin fits within the lineup of standard treatment options. “A lot of people receiving hemodialysis suffer from pruritus and have not been successfully treated. For these individuals difelikefalin could be a game changer,” Dr. Weiner said.

Other nephrologists have a more positive take on the existing treatment options.

“Start systemic therapy for patients with itch that is significantly affecting quality of life; stepping up from topical therapy just delays effective treatment,” advised Hugh C. Rayner, MD, a nephrologist affiliated with Birmingham (England) Heartland’s Hospital who was lead author on a review of pruritus treatments for patients with CKD on hemodialysis.

“Standard systemic therapy is gabapentin or pregabalin,” an approach “supported by robust evidence confirmed in a Cochrane review,” he said in an interview. The impact of difelikefalin “will be limited as its effectiveness in reducing itch is modest at best and far inferior to gabapentin and pregabalin,” Dr. Rayner added. Difelikefalin’s “main downsides will be its cost, compared with gabapentin, and its gastrointestinal side effects.”
 

Adverse-event profiles

In KALM-1, the most frequent adverse effects from difelikefalin treatment was diarrhea, in 10% of patients, compared with a 4% rate among patients who received placebo. Vomiting occurred at a 5% incidence on difelikefalin and in 3% of patients on placebo. All serious adverse events occurred in 26% of patients on difelikefalin and in 22% of those who received placebo. Discontinuations because of an adverse event occurred in 8% of patients on difelikefalin and in 5% of the placebo patients.

An editorial that accompanied the published KALM-1 report in 2020 said “the findings are compelling, although diarrhea, dizziness, and vomiting were frequent side effects.”

Both Dr. Weiner and Dr. Palevsky were more reserved than Dr. Rayner in their appraisal of gabapentin and pregabalin, although Dr. Palevsky admitted that he has prescribed one or the other of these two drugs to “lots of patients,” especially gabapentin. “But they are not completely benign drugs,” he cautioned, a concern echoed by Dr. Weiner.

“Antihistamines, gabapentin, and pregabalin have a high side-effect burden in patients on hemodialysis and limited efficacy, and are poor options for chronic pruritus management,” explained Dr. Weiner. “I would favor difelikefalin to chronic prescription of these other agents” because difelikefalin “appears effective and has a very low side effect burden. Very few effective treatments for pruritus do not have side effects.”

Difelikefalin is a peripherally restricted, selective kappa opioid receptor agonist that exerts antipruritic effects by activating kappa opioid receptors on peripheral neurons and immune cells. The drug’s hydrophilic, small-peptide structure restricts passive diffusion across membranes, which limits the drug’s access to kappa opioid receptors in the central nervous system and hence reduces potential adverse effects.

The FDA made this approval decision without consulting an advisory committee. The companies that will market difelikefalin (Korsuva), Cara Therapeutics and Vifor Pharma, announced that their U.S. promotional launch of the drug starts early in 2022.

The KALM-1 and KALM-2 studies were sponsored by Cara Therapeutics and Vifor Pharma, the two companies that have been jointly developing difelikefalin. Dr. Pavelsky and Dr. Rayner had no relevant disclosures. Dr. Weiner was previously an adviser to Cara and Vifor and participated as an investigator in a difelikefalin clinical study, but more recently has had no relationships with the companies.

[email protected]

The Food and Drug Administration has approved difelikefalin for treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis, the first agent approved from a novel class of kappa opioid receptor agonists.

Olivier Le Moal/Getty Images

Some nephrologists welcomed the Aug. 23 approval of this new option for treating pruritus, a relatively common and often hard-to-resolve complication of dialysis in patients with chronic kidney disease (CKD) that can substantially impinge on quality of life for some patients, but also voiced uncertainty about the role of a new agent with a modest trial track record that may be expensive and face insurance-coverage hurdles.

“Uptake of difelikefalin will depend on awareness of itch among patients dependent on hemodialysis, and on payment policies,” predicted Daniel E. Weiner, MD, a nephrologist at Tufts Medical Center in Boston. “Pruritus is underdiagnosed among people with kidney failure, and in some patients ongoing pruritus can be highly impactful on sleep and quality of life. The clinical trial results were very encouraging that difelikefalin is effective and safe,” which makes recognition of pruritus as a significant issue for patients a key factor in uptake of the new drug, Dr. Weiner, an investigator in a difelikefalin clinical study, said in an interview.

Other nephrologists acknowledged the substantial problem that itch can pose for many patients with CKD on dialysis but questioned the weight of evidence behind difelikefalin’s approval.
 

Two pivotal trials with fewer than 900 total randomized patients

The data considered by the FDA primarily featured results from two pivotal trials, KALM-1 and KALM-2. KALM-1 randomized 378 patients with CKD and on hemodialysis and with moderate to severe pruritus to intravenous treatment with difelikefalin or placebo three times a week for 12 weeks with a primary endpoint of an improvement (decrease) of at least 3 points from baseline in their Worst Itching Intensity Numerical Rating Scale (WI-NRS) score, which averaged just over 7 points at baseline. After 12 weeks on treatment, 52% of patients who received difelikefalin had at least a 3-point drop, compared with 31% of patients who received placebo, a significant difference. The results appeared in a 2020 report in the New England Journal of Medicine.

Confirmatory results came in the second pivotal trial, KALM-2, a similarly designed, 12-week study that randomized 473 patients, with 54% of those in the active arm achieving at least a 3-point cut in their baseline WI-NRS score, compared with 42% of patients who received placebo, a significant difference. A report at the Kidney Week meeting sponsored by the National Kidney Foundation in October 2020 presented the KALM-2 results, but the findings have not yet appeared in a published article.

In sum, the data suggest that treatment with difelikefalin will, on average, produce a clinically meaningful effect on itch compared with placebo in about 20% of patients, with nearly half the patients who receive the active drug having a less robust response and many patients who receive no active treatment also show a meaningful cut in their pruritus severity in a trial setting, noted Paul Palevsky, MD, professor of medicine at the University of Pittsburgh and chief of the renal section at the Veterans Affairs Pittsburgh Healthcare System.

The upshot is that questions linger over which patients are the best candidates for this drug and how it might perform in real-world practice given difelikefalin’s limited track record, Dr. Palevsky said in an interview.

In addition, the labeling specifies the indication is for patients with moderate to severe pruritus, but itching severity is not routinely quantified in these patients in current practice, added Dr. Palevsky, who is also president of the National Kidney Foundation.

Dr. Weiner noted that another unknown is the appropriate duration of treatment in real-world use.
 

What will it cost, and will it be covered?

The drug’s price and insurance coverage will likely be a major factor in uptake of the new drug, agreed both Dr. Weiner and Dr. Palevsky, especially the coverage decision for Medicare patients by the Centers for Medicare & Medicaid Services. A corollary is whether or not coverage for difelikefalin, which patients receive as an intravenous infusion during each of their usual three-times-a-week dialysis sessions, will lie outside of the bundled dialysis reimbursement payment. If is no mechanism exists to pay for difelikefalin separately beyond the current bundled dialysis rate, “I suspect it will not get used very much unless it is very inexpensive,” predicted Dr. Weiner.

Another issue is where difelikefalin fits within the lineup of standard treatment options. “A lot of people receiving hemodialysis suffer from pruritus and have not been successfully treated. For these individuals difelikefalin could be a game changer,” Dr. Weiner said.

Other nephrologists have a more positive take on the existing treatment options.

“Start systemic therapy for patients with itch that is significantly affecting quality of life; stepping up from topical therapy just delays effective treatment,” advised Hugh C. Rayner, MD, a nephrologist affiliated with Birmingham (England) Heartland’s Hospital who was lead author on a review of pruritus treatments for patients with CKD on hemodialysis.

“Standard systemic therapy is gabapentin or pregabalin,” an approach “supported by robust evidence confirmed in a Cochrane review,” he said in an interview. The impact of difelikefalin “will be limited as its effectiveness in reducing itch is modest at best and far inferior to gabapentin and pregabalin,” Dr. Rayner added. Difelikefalin’s “main downsides will be its cost, compared with gabapentin, and its gastrointestinal side effects.”
 

Adverse-event profiles

In KALM-1, the most frequent adverse effects from difelikefalin treatment was diarrhea, in 10% of patients, compared with a 4% rate among patients who received placebo. Vomiting occurred at a 5% incidence on difelikefalin and in 3% of patients on placebo. All serious adverse events occurred in 26% of patients on difelikefalin and in 22% of those who received placebo. Discontinuations because of an adverse event occurred in 8% of patients on difelikefalin and in 5% of the placebo patients.

An editorial that accompanied the published KALM-1 report in 2020 said “the findings are compelling, although diarrhea, dizziness, and vomiting were frequent side effects.”

Both Dr. Weiner and Dr. Palevsky were more reserved than Dr. Rayner in their appraisal of gabapentin and pregabalin, although Dr. Palevsky admitted that he has prescribed one or the other of these two drugs to “lots of patients,” especially gabapentin. “But they are not completely benign drugs,” he cautioned, a concern echoed by Dr. Weiner.

“Antihistamines, gabapentin, and pregabalin have a high side-effect burden in patients on hemodialysis and limited efficacy, and are poor options for chronic pruritus management,” explained Dr. Weiner. “I would favor difelikefalin to chronic prescription of these other agents” because difelikefalin “appears effective and has a very low side effect burden. Very few effective treatments for pruritus do not have side effects.”

Difelikefalin is a peripherally restricted, selective kappa opioid receptor agonist that exerts antipruritic effects by activating kappa opioid receptors on peripheral neurons and immune cells. The drug’s hydrophilic, small-peptide structure restricts passive diffusion across membranes, which limits the drug’s access to kappa opioid receptors in the central nervous system and hence reduces potential adverse effects.

The FDA made this approval decision without consulting an advisory committee. The companies that will market difelikefalin (Korsuva), Cara Therapeutics and Vifor Pharma, announced that their U.S. promotional launch of the drug starts early in 2022.

The KALM-1 and KALM-2 studies were sponsored by Cara Therapeutics and Vifor Pharma, the two companies that have been jointly developing difelikefalin. Dr. Pavelsky and Dr. Rayner had no relevant disclosures. Dr. Weiner was previously an adviser to Cara and Vifor and participated as an investigator in a difelikefalin clinical study, but more recently has had no relationships with the companies.

[email protected]

Alcohol use is a known risk factor for gastrointestinal (GI) cancers. Now, new research indicates that this risk is more associated with frequent drinking – even in smaller amounts – compared with higher amounts or binge drinking, given similar weekly levels.

“The novel finding of the current study is that frequent drinking may be more dangerous than binge drinking with regard to GI cancers. Alcohol use is a known risk factor for gastrointestinal (GI) cancers. Now, new research indicates that this risk is more associated with frequent drinking – even in smaller amounts -- compared with higher amounts or binge drinking, given similar weekly levels.” first author Jung Eun Yook, MD, of Seoul (South Korea) National University Hospital, and colleagues reported in an article published Aug. 18, 2021, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2021.20382).

“This finding suggests that repeated alcohol consumption events even at lower amounts of alcohol may have a greater carcinogenic effect on GI organs than the consumption of larger amounts of alcohol at a lower frequency,” the investigators wrote.

A possible reason behind the difference in risk may be that the chronic “carcinogenic insult” from regular alcohol use may promote cancer development, whereas less frequent, episodic alcohol exposures may allow physiologic recovery, said the authors.

The results are from a population-based study that involved 11,737,467 participants in the Korean National Health System database who did not have cancer and who took part in a national screening program between January 2009 and December 2010.

They were followed from the year after their screening until either they had received a diagnosis of a GI cancer, death occurred, or the end of December 2017.

During a median follow-up of 6.4 years, 319,202 (2.7%) of those in the study developed a GI cancer.

The increase in the risk associated with alcohol consumption was dose dependent.

Compared with those who did not consume alcohol, the risk of developing GI cancer was higher for mild drinkers (adjusted hazard ratio, 1.04; 95% confidence interval, 1.03-1.05), moderate drinkers (aHR, 1.14; 95% CI, 1.12-1.15), and heavy drinkers (aHR, 1.28; 95% CI, 1.26-1.29), after adjusting for age, sex, income, smoking status with intensity, regular exercise, body mass index, diabetes, hypertension, and dyslipidemia.

There was a linear association between the frequency of drinking and GI cancer risk, with an aHR of 1.39 for individuals who reported drinking every day (95% CI, 1.36-1.41). The risk for GI cancer increased with consumption of five to seven units per occasion (aHR, 1.15). Notably, there were no similar increases with higher intake, including intake of 8-14 units per occasion (aHR, 1.11; 95% CI, 1.09-1.12), and even up to more than 14 units per occasion (aHR, 1.11; 95%CI, 1.08-1.14), in comparison with an intake of 5-7 units per occasion.

“Given similar weekly alcohol consumption levels, the risk of GI cancer increased with a higher frequency of drinking and decreased with a higher amount per occasion,” the authors write.

“Most previous studies just assess alcohol consumption as a total amount, [such as] drinks per occasion times occasion per week equals drinks per week [and] grams per week,” coauthor Dong Wook Shin, MD, DrPH, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, said in an interview.

“But it was not known whether frequent drinking with small amount is more harmful than binge drinking, given a similar level of total drinking,” Dr. Shin said.

The increased risk associated with frequent drinking was generally similar with respect to esophageal, gastric, colorectal, biliary, and pancreatic cancer.

An exception was liver cancer, which showed a slightly decreased risk among mild drinkers (aHR, 0.91; 95% CI, 0.89-0.93).

Of note, the association between alcohol intake and the incidence of GI cancer was lower among women than men in terms of weekly consumption, frequency, and amount of alcohol consumed per occasion.

The associations between drinking and cancer type in terms of esophageal and liver cancers were similar between men and women. However, the alcohol-related risk for colorectal, biliary, and pancreatic cancers was less prominent for women.

Possible mechanisms related to regular drinking

A factor that might account for the increase in GI cancer risk with frequent drinking is that regular alcohol consumption “promotes the accumulation of cell divisions in the stem cells that maintain tissues in homeostasis,” the authors explained.

Another possible explanation is that long-term alcohol exposure may promote carcinogenesis, whereas less frequent exposure might allow “physiological homeostasis,” the authors wrote, adding that in vivo experiments have shown that duration and dose of alcohol exposure have been linked to cancer development.

Importantly, the findings support the importance of reducing the frequency of alcohol use to prevent cancer, the authors noted.

“Alcohol users who have a glass of wine or beer during dinner every day may develop more cancer than people who occasionally consume several drinks,” they cautioned.
 

Genetics, self-reporting considerations

In a related commentary, John D. Potter, MBBS, PhD, of the Research Center for Hauora and Health, Massey University, Wellington, New Zealand, noted that, in addition to supporting the known link between alcohol and cancers of the esophagus, colorectum, and liver, the study “strengthens evidence for a role of alcohol in stomach, biliary tract, and pancreas cancers.”

In comparison with nondrinkers, those who reported heavy drinking were much more likely to be smokers (51.6% vs. 9.0%); however, the study adjusted for smoking.

“Because the researchers were able to control for tobacco, this last finding [regarding the association with cancers of the stomach, biliary tract, and pancreas] is particularly informative,” Dr. Potter noted.

An important caveat is that more than a quarter of the Korean population is known to have an inactive form of the aldehyde dehydrogenase gene (ALDH2), which could have effects on alcohol metabolism as well as the risk for cancer, Dr. Potter wrote.

“This common polymorphism in ALDH2 (ALDH2 rs671 [c.1510G>A (Glu504Lys)]) has paradoxical effects,” he wrote.

“It increases the level of acetaldehyde in the blood of drinkers, which in turn increases the risk of cancer because acetaldehyde is a key player in the carcinogenicity of alcoholic beverages,” Dr. Potter explained. “On the other hand, the accumulation of acetaldehyde and the resultant flushing response are sufficiently unpleasant that they tend to reduce alcohol consumption among those with the Lys allele.”

The study results may therefore not be generalizable to a population in which the distribution of the variation in the ALDH2 enzyme differs, Dr. Potter added.

The lower prevalence of the inactive form (in North America, for instance) would mean that this lower prevalence was not a constraint on individuals’ drinking behavior as it is for some in Korea, Dr. Potter explained.

He noted another consideration: the underreporting of alcohol use is a well-known limitation of studies involving the assessment of alcohol consumption.

Dr. Shin agreed that underreporting is a limitation.

“People tend to underestimate their alcohol use,” Dr. Shin said in an interview.

However, he noted that “our study participants are health-screening participants aged 40 years and older, [and] people who participate in health screening tend to have higher awareness and better health behavior than nonparticipants.”

The authors and Dr. Potter disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Alcohol use is a known risk factor for gastrointestinal (GI) cancers. Now, new research indicates that this risk is more associated with frequent drinking – even in smaller amounts – compared with higher amounts or binge drinking, given similar weekly levels.

“The novel finding of the current study is that frequent drinking may be more dangerous than binge drinking with regard to GI cancers. Alcohol use is a known risk factor for gastrointestinal (GI) cancers. Now, new research indicates that this risk is more associated with frequent drinking – even in smaller amounts -- compared with higher amounts or binge drinking, given similar weekly levels.” first author Jung Eun Yook, MD, of Seoul (South Korea) National University Hospital, and colleagues reported in an article published Aug. 18, 2021, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2021.20382).

“This finding suggests that repeated alcohol consumption events even at lower amounts of alcohol may have a greater carcinogenic effect on GI organs than the consumption of larger amounts of alcohol at a lower frequency,” the investigators wrote.

A possible reason behind the difference in risk may be that the chronic “carcinogenic insult” from regular alcohol use may promote cancer development, whereas less frequent, episodic alcohol exposures may allow physiologic recovery, said the authors.

The results are from a population-based study that involved 11,737,467 participants in the Korean National Health System database who did not have cancer and who took part in a national screening program between January 2009 and December 2010.

They were followed from the year after their screening until either they had received a diagnosis of a GI cancer, death occurred, or the end of December 2017.

During a median follow-up of 6.4 years, 319,202 (2.7%) of those in the study developed a GI cancer.

The increase in the risk associated with alcohol consumption was dose dependent.

Compared with those who did not consume alcohol, the risk of developing GI cancer was higher for mild drinkers (adjusted hazard ratio, 1.04; 95% confidence interval, 1.03-1.05), moderate drinkers (aHR, 1.14; 95% CI, 1.12-1.15), and heavy drinkers (aHR, 1.28; 95% CI, 1.26-1.29), after adjusting for age, sex, income, smoking status with intensity, regular exercise, body mass index, diabetes, hypertension, and dyslipidemia.

There was a linear association between the frequency of drinking and GI cancer risk, with an aHR of 1.39 for individuals who reported drinking every day (95% CI, 1.36-1.41). The risk for GI cancer increased with consumption of five to seven units per occasion (aHR, 1.15). Notably, there were no similar increases with higher intake, including intake of 8-14 units per occasion (aHR, 1.11; 95% CI, 1.09-1.12), and even up to more than 14 units per occasion (aHR, 1.11; 95%CI, 1.08-1.14), in comparison with an intake of 5-7 units per occasion.

“Given similar weekly alcohol consumption levels, the risk of GI cancer increased with a higher frequency of drinking and decreased with a higher amount per occasion,” the authors write.

“Most previous studies just assess alcohol consumption as a total amount, [such as] drinks per occasion times occasion per week equals drinks per week [and] grams per week,” coauthor Dong Wook Shin, MD, DrPH, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, said in an interview.

“But it was not known whether frequent drinking with small amount is more harmful than binge drinking, given a similar level of total drinking,” Dr. Shin said.

The increased risk associated with frequent drinking was generally similar with respect to esophageal, gastric, colorectal, biliary, and pancreatic cancer.

An exception was liver cancer, which showed a slightly decreased risk among mild drinkers (aHR, 0.91; 95% CI, 0.89-0.93).

Of note, the association between alcohol intake and the incidence of GI cancer was lower among women than men in terms of weekly consumption, frequency, and amount of alcohol consumed per occasion.

The associations between drinking and cancer type in terms of esophageal and liver cancers were similar between men and women. However, the alcohol-related risk for colorectal, biliary, and pancreatic cancers was less prominent for women.

Possible mechanisms related to regular drinking

A factor that might account for the increase in GI cancer risk with frequent drinking is that regular alcohol consumption “promotes the accumulation of cell divisions in the stem cells that maintain tissues in homeostasis,” the authors explained.

Another possible explanation is that long-term alcohol exposure may promote carcinogenesis, whereas less frequent exposure might allow “physiological homeostasis,” the authors wrote, adding that in vivo experiments have shown that duration and dose of alcohol exposure have been linked to cancer development.

Importantly, the findings support the importance of reducing the frequency of alcohol use to prevent cancer, the authors noted.

“Alcohol users who have a glass of wine or beer during dinner every day may develop more cancer than people who occasionally consume several drinks,” they cautioned.
 

Genetics, self-reporting considerations

In a related commentary, John D. Potter, MBBS, PhD, of the Research Center for Hauora and Health, Massey University, Wellington, New Zealand, noted that, in addition to supporting the known link between alcohol and cancers of the esophagus, colorectum, and liver, the study “strengthens evidence for a role of alcohol in stomach, biliary tract, and pancreas cancers.”

In comparison with nondrinkers, those who reported heavy drinking were much more likely to be smokers (51.6% vs. 9.0%); however, the study adjusted for smoking.

“Because the researchers were able to control for tobacco, this last finding [regarding the association with cancers of the stomach, biliary tract, and pancreas] is particularly informative,” Dr. Potter noted.

An important caveat is that more than a quarter of the Korean population is known to have an inactive form of the aldehyde dehydrogenase gene (ALDH2), which could have effects on alcohol metabolism as well as the risk for cancer, Dr. Potter wrote.

“This common polymorphism in ALDH2 (ALDH2 rs671 [c.1510G>A (Glu504Lys)]) has paradoxical effects,” he wrote.

“It increases the level of acetaldehyde in the blood of drinkers, which in turn increases the risk of cancer because acetaldehyde is a key player in the carcinogenicity of alcoholic beverages,” Dr. Potter explained. “On the other hand, the accumulation of acetaldehyde and the resultant flushing response are sufficiently unpleasant that they tend to reduce alcohol consumption among those with the Lys allele.”

The study results may therefore not be generalizable to a population in which the distribution of the variation in the ALDH2 enzyme differs, Dr. Potter added.

The lower prevalence of the inactive form (in North America, for instance) would mean that this lower prevalence was not a constraint on individuals’ drinking behavior as it is for some in Korea, Dr. Potter explained.

He noted another consideration: the underreporting of alcohol use is a well-known limitation of studies involving the assessment of alcohol consumption.

Dr. Shin agreed that underreporting is a limitation.

“People tend to underestimate their alcohol use,” Dr. Shin said in an interview.

However, he noted that “our study participants are health-screening participants aged 40 years and older, [and] people who participate in health screening tend to have higher awareness and better health behavior than nonparticipants.”

The authors and Dr. Potter disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Alcohol use is a known risk factor for gastrointestinal (GI) cancers. Now, new research indicates that this risk is more associated with frequent drinking – even in smaller amounts – compared with higher amounts or binge drinking, given similar weekly levels.

“The novel finding of the current study is that frequent drinking may be more dangerous than binge drinking with regard to GI cancers. Alcohol use is a known risk factor for gastrointestinal (GI) cancers. Now, new research indicates that this risk is more associated with frequent drinking – even in smaller amounts -- compared with higher amounts or binge drinking, given similar weekly levels.” first author Jung Eun Yook, MD, of Seoul (South Korea) National University Hospital, and colleagues reported in an article published Aug. 18, 2021, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2021.20382).

“This finding suggests that repeated alcohol consumption events even at lower amounts of alcohol may have a greater carcinogenic effect on GI organs than the consumption of larger amounts of alcohol at a lower frequency,” the investigators wrote.

A possible reason behind the difference in risk may be that the chronic “carcinogenic insult” from regular alcohol use may promote cancer development, whereas less frequent, episodic alcohol exposures may allow physiologic recovery, said the authors.

The results are from a population-based study that involved 11,737,467 participants in the Korean National Health System database who did not have cancer and who took part in a national screening program between January 2009 and December 2010.

They were followed from the year after their screening until either they had received a diagnosis of a GI cancer, death occurred, or the end of December 2017.

During a median follow-up of 6.4 years, 319,202 (2.7%) of those in the study developed a GI cancer.

The increase in the risk associated with alcohol consumption was dose dependent.

Compared with those who did not consume alcohol, the risk of developing GI cancer was higher for mild drinkers (adjusted hazard ratio, 1.04; 95% confidence interval, 1.03-1.05), moderate drinkers (aHR, 1.14; 95% CI, 1.12-1.15), and heavy drinkers (aHR, 1.28; 95% CI, 1.26-1.29), after adjusting for age, sex, income, smoking status with intensity, regular exercise, body mass index, diabetes, hypertension, and dyslipidemia.

There was a linear association between the frequency of drinking and GI cancer risk, with an aHR of 1.39 for individuals who reported drinking every day (95% CI, 1.36-1.41). The risk for GI cancer increased with consumption of five to seven units per occasion (aHR, 1.15). Notably, there were no similar increases with higher intake, including intake of 8-14 units per occasion (aHR, 1.11; 95% CI, 1.09-1.12), and even up to more than 14 units per occasion (aHR, 1.11; 95%CI, 1.08-1.14), in comparison with an intake of 5-7 units per occasion.

“Given similar weekly alcohol consumption levels, the risk of GI cancer increased with a higher frequency of drinking and decreased with a higher amount per occasion,” the authors write.

“Most previous studies just assess alcohol consumption as a total amount, [such as] drinks per occasion times occasion per week equals drinks per week [and] grams per week,” coauthor Dong Wook Shin, MD, DrPH, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, said in an interview.

“But it was not known whether frequent drinking with small amount is more harmful than binge drinking, given a similar level of total drinking,” Dr. Shin said.

The increased risk associated with frequent drinking was generally similar with respect to esophageal, gastric, colorectal, biliary, and pancreatic cancer.

An exception was liver cancer, which showed a slightly decreased risk among mild drinkers (aHR, 0.91; 95% CI, 0.89-0.93).

Of note, the association between alcohol intake and the incidence of GI cancer was lower among women than men in terms of weekly consumption, frequency, and amount of alcohol consumed per occasion.

The associations between drinking and cancer type in terms of esophageal and liver cancers were similar between men and women. However, the alcohol-related risk for colorectal, biliary, and pancreatic cancers was less prominent for women.

Possible mechanisms related to regular drinking

A factor that might account for the increase in GI cancer risk with frequent drinking is that regular alcohol consumption “promotes the accumulation of cell divisions in the stem cells that maintain tissues in homeostasis,” the authors explained.

Another possible explanation is that long-term alcohol exposure may promote carcinogenesis, whereas less frequent exposure might allow “physiological homeostasis,” the authors wrote, adding that in vivo experiments have shown that duration and dose of alcohol exposure have been linked to cancer development.

Importantly, the findings support the importance of reducing the frequency of alcohol use to prevent cancer, the authors noted.

“Alcohol users who have a glass of wine or beer during dinner every day may develop more cancer than people who occasionally consume several drinks,” they cautioned.
 

Genetics, self-reporting considerations

In a related commentary, John D. Potter, MBBS, PhD, of the Research Center for Hauora and Health, Massey University, Wellington, New Zealand, noted that, in addition to supporting the known link between alcohol and cancers of the esophagus, colorectum, and liver, the study “strengthens evidence for a role of alcohol in stomach, biliary tract, and pancreas cancers.”

In comparison with nondrinkers, those who reported heavy drinking were much more likely to be smokers (51.6% vs. 9.0%); however, the study adjusted for smoking.

“Because the researchers were able to control for tobacco, this last finding [regarding the association with cancers of the stomach, biliary tract, and pancreas] is particularly informative,” Dr. Potter noted.

An important caveat is that more than a quarter of the Korean population is known to have an inactive form of the aldehyde dehydrogenase gene (ALDH2), which could have effects on alcohol metabolism as well as the risk for cancer, Dr. Potter wrote.

“This common polymorphism in ALDH2 (ALDH2 rs671 [c.1510G>A (Glu504Lys)]) has paradoxical effects,” he wrote.

“It increases the level of acetaldehyde in the blood of drinkers, which in turn increases the risk of cancer because acetaldehyde is a key player in the carcinogenicity of alcoholic beverages,” Dr. Potter explained. “On the other hand, the accumulation of acetaldehyde and the resultant flushing response are sufficiently unpleasant that they tend to reduce alcohol consumption among those with the Lys allele.”

The study results may therefore not be generalizable to a population in which the distribution of the variation in the ALDH2 enzyme differs, Dr. Potter added.

The lower prevalence of the inactive form (in North America, for instance) would mean that this lower prevalence was not a constraint on individuals’ drinking behavior as it is for some in Korea, Dr. Potter explained.

He noted another consideration: the underreporting of alcohol use is a well-known limitation of studies involving the assessment of alcohol consumption.

Dr. Shin agreed that underreporting is a limitation.

“People tend to underestimate their alcohol use,” Dr. Shin said in an interview.

However, he noted that “our study participants are health-screening participants aged 40 years and older, [and] people who participate in health screening tend to have higher awareness and better health behavior than nonparticipants.”

The authors and Dr. Potter disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The United States could get the COVID-19 pandemic under control by the spring of 2022 if enough Americans become vaccinated, Anthony S. Fauci, MD, said.

Speaking to Anderson Cooper on CNN, Dr. Fauci corrected the timeline he gave in an interview earlier with Mary Louise Kelly of NPR.

In the NPR interview, he had said that if “the overwhelming majority of the people vaccinated, I think as we get into the fall and the winter, we could start to really get some good control over this as we get into 2022.”

Dr. Fauci told Mr. Cooper that he listened to a recording of the NPR interview later and realized his mistake.

“I meant to say the spring of 2022,” Dr. Fauci told CNN. “I misspoke. My bad.”

Dr. Fauci, the head of the National Institute of Allergy and Infectious Diseases and the chief White House medical adviser, said the pandemic will be under control when the large majority of Americans have gotten vaccinated or been infected with COVID-19 and recovered, which offers some protection against the virus.

People who have been infected and recovered should still get vaccinated, he said.

“The degree of protection you could induce in someone who’s been infected and then recovered and then vaccinated is an enormous increase in the degree of protection,” Dr. Fauci said.

“I think we can get a degree of overall blanket protection of the community that as we get into the early part of 2022 ... we could start getting back to a degree of normality.”

A version of this article first appeared on WebMD.com.

The United States could get the COVID-19 pandemic under control by the spring of 2022 if enough Americans become vaccinated, Anthony S. Fauci, MD, said.

Speaking to Anderson Cooper on CNN, Dr. Fauci corrected the timeline he gave in an interview earlier with Mary Louise Kelly of NPR.

In the NPR interview, he had said that if “the overwhelming majority of the people vaccinated, I think as we get into the fall and the winter, we could start to really get some good control over this as we get into 2022.”

Dr. Fauci told Mr. Cooper that he listened to a recording of the NPR interview later and realized his mistake.

“I meant to say the spring of 2022,” Dr. Fauci told CNN. “I misspoke. My bad.”

Dr. Fauci, the head of the National Institute of Allergy and Infectious Diseases and the chief White House medical adviser, said the pandemic will be under control when the large majority of Americans have gotten vaccinated or been infected with COVID-19 and recovered, which offers some protection against the virus.

People who have been infected and recovered should still get vaccinated, he said.

“The degree of protection you could induce in someone who’s been infected and then recovered and then vaccinated is an enormous increase in the degree of protection,” Dr. Fauci said.

“I think we can get a degree of overall blanket protection of the community that as we get into the early part of 2022 ... we could start getting back to a degree of normality.”

A version of this article first appeared on WebMD.com.

The United States could get the COVID-19 pandemic under control by the spring of 2022 if enough Americans become vaccinated, Anthony S. Fauci, MD, said.

Speaking to Anderson Cooper on CNN, Dr. Fauci corrected the timeline he gave in an interview earlier with Mary Louise Kelly of NPR.

In the NPR interview, he had said that if “the overwhelming majority of the people vaccinated, I think as we get into the fall and the winter, we could start to really get some good control over this as we get into 2022.”

Dr. Fauci told Mr. Cooper that he listened to a recording of the NPR interview later and realized his mistake.

“I meant to say the spring of 2022,” Dr. Fauci told CNN. “I misspoke. My bad.”

Dr. Fauci, the head of the National Institute of Allergy and Infectious Diseases and the chief White House medical adviser, said the pandemic will be under control when the large majority of Americans have gotten vaccinated or been infected with COVID-19 and recovered, which offers some protection against the virus.

People who have been infected and recovered should still get vaccinated, he said.

“The degree of protection you could induce in someone who’s been infected and then recovered and then vaccinated is an enormous increase in the degree of protection,” Dr. Fauci said.

“I think we can get a degree of overall blanket protection of the community that as we get into the early part of 2022 ... we could start getting back to a degree of normality.”

A version of this article first appeared on WebMD.com.

There will be so much more to the annual congress of the European Society of Cardiology, which begins Aug. 27 with an all-virtual format, than detailed primary results of EMPEROR-Preserved, a trial that could mark a turning point for heart failure (HF) medical therapy.

Also among the featured Hot Line and Late-Breaking Science sessions are – along with many other studies – explorations of arrhythmia management (ablation or guided by loop recorder); secondary prevention, including by vaccination; oral anticoagulation, notably after transcatheter valve procedures; and colchicine or thrombosis prophylaxis in hospitalized patients with COVID-19.

There will even be a head-to-head comparison of two long-familiar left atrial appendage (LAA) occluders, and a population-based, randomized trial of sodium restriction through wide-scale use of a potassium-based salt substitute.

The congress will also introduce four guideline documents at sessions throughout the Congress, one on each day. They cover new and modified recommendations for heart failure; pacing, including cardiac resynchronization therapy (CRT); cardiovascular (CV) disease prevention; and, with cosponsorship from the European Association for Cardio-Thoracic Surgery, valvular heart disease.
 

The virtues of virtual

That next year’s Congress is slated for Aug. 27-30 in Barcelona should be welcome news for anyone whose “what if” curiosity about all-virtual conferences has already been satisfied. But with experience comes wisdom, as the medical societies have learned that online scientific meetings have some winning qualities that may be worth keeping, as least for a while.

“I think there is no doubt that the digital format will continue, for several reasons. One is that this pandemic is not over,” ESC Congress program committee chair Stephan Windecker, MD, Bern (Switzerland) University Hospital, , told this news organization. “As long as it is not over, the digital format is here to stay.”

But it also appears that people who haven’t been able to attend the congress in person are keen to log in and engage online, Dr. Windecker said. The 2020 all-virtual conference drew a much younger pool of registrants, on average, than did the live conferences before the pandemic.

“I think that’s an indication of people that may be in training, in early stages of their career, or they don’t have the support from departments or from their practice, or other financial means.” But they are able to participate via computer, tablet, or smartphone, he said.

“Another advantage is that the recorded content can be replayed at the convenience of whoever wants to consume it at a later point in time,” he added. “Those are just some examples why the digital format is likely to stay,” on its own or in a new age of hybrid meetings.  
 

New and updated guidelines

Leading off the guideline series is the document on diagnosis and treatment of acute and chronic HF, which leveraged the past few busy years of HF clinical trials to arrive at a number of new recommendations and strengthened level-of-evidence ratings. It covers both drug and device therapy of HF with reduced ejection fraction (HFrEF) and acute decompensated HF, and tweaks and further enshrines the concept of HF with mildly reduced ejection fraction (HFmrEF).

Several updated recommendations for both long-used and novel medications, notably the sodium-glucose cotransporter 2 inhibitors, will be included because of the recently appreciated evidence-based impact in HFrEF, Dr. Windecker noted.

“I think it will be particularly interesting to look for the SGLT2 inhibitors as not a completely new class of drugs, but certainly one where there has been a lot of new evidence, to look at how those drugs will be integrated in the overall care pathway.”

A top-line preview of the new HF guideline limited to drug therapy, presented at July’s Heart Failure Association of the European Society of Cardiology (ESC-HFA), provided a simple answer to a common question in the new, bountiful age of HFrEF medications: Which meds, initiated in what order?

As it happens, the new recommendation for first-line HFrEF drug therapy is not a silver bullet, but a shotgun – prompt initiation of at least four meds, one from each of four drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors. Each class, as described in the document, is to be started as soon as safely feasible, in a sequence deemed appropriate for each individual patient.
 

Spotlight on EMPEROR-Preserved

The world already knows that the trial, which tested the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) on top of standard therapy, “met” its primary endpoint in almost 6,000 patients with HF with preserved ejection fraction (HFpEF), who included some with HFmrEF by more contemporary definitions.

That means patients in EMPEROR-Preserved assigned to take empagliflozin showed significantly fewer events that made up the study’s primary endpoint, a composite of CV death or HF hospitalization. It appears to be the first clearly significant overall medical therapy benefit for a clinical primary endpoint in a major randomized HFpEF drug trial.

And that, pending fuller presentation of trial results at the Congress on Aug. 27, could be a huge deal for the half of HF patients with left ventricular ejection fractions (LVEF) higher than the HFrEF range.

Those early top-line results weren’t a decisive bombshell for a field now filled with hope for a practice-changing empagliflozin outcome in EMPEROR-Preserved, which isn’t a certainty. They were more like the “boom” of a mortar launching a rocket of fireworks that may explode into a chrysanthemum or green comet or, sometimes, turn out to be no more than a dud. The promise of the early cursory results critically depends on further details.

“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades,” Mikhail N. Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said.

“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don’t know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalizations and cardiovascular death, or only one of the two.”

For example: “If we see an impressive benefit for reduction of hospitalizations, but not a significant reduction in death, that would still be a huge advance. That’s because, to date, we don’t have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalization or improvement in symptoms, function, or quality of life,” observed Dr. Kosiborod, who wasn’t part of EMPEROR-Preserved.

There have been “suggestions” from HFrEF trials that empagliflozin and dapagliflozin (Farxiga, AstraZeneca) “have very comparable effects on at least the endpoint of cardiovascular death or hospitalization for heart failure,” he said. “So, my expectation would be that whatever is observed in EMPEROR-Preserved is likely a class effect, as well.”

Following EMPEROR-Preserved on the agenda is EMPEROR-Pooled, a patient-level combined analysis of the EMPEROR series of trials that spans the range of HF, regardless of ejection fraction or diabetes status, primarily exploring the effects of empagliflozin on renal function.
 

Other offerings, Friday, Aug. 27

Scheduled immediately after EMPEROR-Preserved is a presentation on the SMART-MI trial, which should clarify whether management guided by continuous ambulatory monitoring is effective in patients considered at especially high arrhythmic risk. Entry called for recent myocardial infarction and an LVEF of 36%-50% with evidence of cardiac autonomic dysfunction.

The trial randomly assigned 400 such patients to be or not be implanted with a Reveal LINQ (Medtronic) loop recorder and followed them for up to 18 months, primarily for detection of potentially serious arrhythmic events. Endpoints that involved mortality, hospitalization or other clinical events were secondary.

In a time slot preceding both SMART-MI and EMPEROR-Preserved, the GUIDE-HF trial is following a projected 3,600 patients with HF implanted with a CardioMEMS HF System (Abbott) pulmonary artery (PA) pressure sensor to explore the its value for guiding management.

The trial’s three cohorts, followed for at least 12 months, include randomized sensor-monitored and control groups of patients with New York Heart Association class 2-4 symptoms, as well as a third observational set of patients in NYHA class 3. That’s the indication for which the CardioMEMS monitor gained approval in the United States in 2014 based on the 2011 CHAMPION trial, and which fared just as well in the 2017 CHAMPION Post-Approval Study.

The Friday Hot Lines also include Dal-GenE, which has entered about 6,000 patients with recent MI to test the once-abandoned cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DalCor) for any secondary-prevention benefits when used selectively. The trial’s hook: All its patients are confirmed to have the AA genotype of the rs1967309 variant in the ADCY9 gene, which has been associated with a pronounced clinical response to CETP inhibition.

Saturday, Aug. 28

The direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in patients with nonvalvular atrial fibrillation (AFib). But whether DOACs are similarly preferable in the growing world population of people who have undergone transcatheter aortic valve replacement (TAVR or TAVI), an issue explored with variable results in the ATLANTIS and GALILEO trials, is far from settled.

The ENVISAGE-TAVI AF trial explored the question for the factor X inhibitor edoxaban (Savaysa, Lixiana, Daiichi-Sankyo) in 1,400 patients with AFib and a transfemoral TAVR in the previous 5 days, who were randomly assigned to the DOAC or standard management along with discretionary antiplatelet therapy. They’ve been followed for up to 3 years for a composite endpoint of clinical events – including death, MI, and stroke – and for major bleeding.

The day will also feature MASTER DAPT, a comparison of two dual-antiplatelet therapy (DAPT) regimens in an estimated 4,300 patients considered to be high-risk for bleeding who had received the sirolimus-eluting Ultimaster (Terumo) coronary stent, which has a bioresorbable polymer coating.

Investigators have randomly assigned patients to receive either very-short-duration DAPT, for about a month after stenting, followed by a P2Y12 inhibitor alone for up to a year after the procedure; or a more conventional regimen of a P2Y12 inhibitor for 6-12 months with aspirin maintained for a total of 12 months.

Later that day, investigators from the FIGARO-DKD trial will present their results based on 7,437 patients with type 2 diabetes and chronic kidney disease (CKD), a much fuller version than the top-line findings announced by sponsor Bayer 3 months ago.

Those top-line results suggested that patients assigned to receive the nonsteroidal nonselective mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) on top of standard care benefited with a drop in risk for the primary endpoint of CV death or nonfatal CV events.

Finerenone was recently approved in the United States for treating patients with both type 2 diabetes and CKD based on the published FIDELIO-DKD trial, which had seen less CKD progression and fewer CV events in such patients who took the novel MRA.

Although similar in design to FIGARO-DKD, FIDELIO-DKD had entered fewer patients with early-stage diabetic kidney disease (DKD). That led researchers to pool the two trials’ populations to create a cohort that spans the spectrum of DKD severity. An analysis of the pooled cohort, dubbed FIDELITY, is on the schedule after FIGARO-DKD.

After FIDELITY is the prospective APAF-CRT trial that is following a projected 1,830 patients with permanent, symptomatic AFib and a recent hospitalization for AFib or HF and who were not good candidates for standard ablation. They were assigned to receive either atrioventricular junctional ablation followed by CRT, with or without a defibrillation, on top of optimal meds – a so-called “ablate-and-pace” strategy – or an implantable cardioverter defibrillator with rate-control drug therapy.

The new analysis represents the trial’s second phase in which mortality was followed for 4 years as the primary endpoint, in contrast to the previously reported initial phase that followed the first 102 patients for 2 years for the composite primary endpoint of death, worsening HF, and HF hospitalization. The first phase had halted enrollment before reaching its planned target of 280 patients after an interim analysis showed a significant benefit for ablate and pace. 

Next up: DECAAF 2, a randomized assessment of whether catheter ablation for AFib guided by delayed gadolinium enhancement on MRI, a proxy for scar tissue, can be more effective than standard AFib ablation by pulmonary vein isolation alone. An estimated 900 patients with persistent AFib who had never before undergone ablation for the arrhythmia were randomly assigned to one strategy or the other and followed for AFib recurrence over 18 months.
 

Sunday, Aug. 29

The TOMAHAWK trial aimed to clarify the optimal timing of invasive coronary angiography for resuscitated patients with non–ST-segment elevation out-of-hospital cardiac arrest, a broad population in a setting for which there is little randomized-trial guidance. Investigators randomly assigned 558 such patients to undergo immediate invasive angiography or to direct intensive care unit admission for initial standard care with discretionary delayed angiography. Patients were followed for all-cause mortality, with other clinical events and neurologic outcomes as secondary endpoints.

Next on the schedule, the RIPCORD-2 trial randomly assigned 1,100 patients with stable known or suspected coronary artery disease (CAD) to undergo conventional angiography alone or with added direct pressure-wire measurement of fractional flow reserve to guide management decisions. Primary outcomes include health care costs and patient-reported quality of life at 1 year.

Slated for later that day, the Asymptomatic Carotid Surgery Trial-2 (ACST-2) has entered an estimated 3600 patients with a substantial carotid artery narrowing not associated with symptoms but for which either carotid endarterectomy (CEA) or carotid artery stenting (CAS) was considered anatomically feasible. There also must have been “substantial uncertainty” regarding the optimal procedure choice.

The trial, conducted in 40 countries primarily in Europe and North America and launched in 2008, randomly assigned the patients to undergo either CEA or CAS, in both cases with appropriate medical therapy, and followed them for periprocedural events and up to 10 years for strokes and stroke-related events.

The LOOP study, which is to directly follow ACST-2, has explored whether screening for AFib using the Medtronic Reveal LINQ monitor in older patients with non-AFib stroke risk factors – with oral anticoagulation prescribed for those who test positive – can lower their risk for stroke or systemic embolism. It randomly assigned 6,000 such patients to care guided by the loop recorder or to standard care.

On a somewhat larger scale, the Salt Substitute and Stroke Study (SSaSS) randomly assigned a total of 20,996 people in about 600 villages across northern China and Tibet to sodium-restriction intervention and control groups by village. All participants had a history of stroke or were aged at least 60 years with uncontrolled hypertension.

As described by the trial’s online portal, participants in villages assigned to the intervention group were given a supply of a low-sodium, potassium-supplementing salt substitute to replace their own salt supplies, along with education on the health benefits of sodium restriction. Participants in control villages continued their normal diets and, at the trial’s beginning, received “advice to reduce their salt intake.” All were required to own a telephone.

Clinical events, including strokes and hospitalizations throughout a 5-year follow-up, were tracked by phone calls made to all participants every 6 months and were documented at follow-up home visits.

Sunday is also to feature a Late-Breaking Trials session with a focus on COVID-19, which leads off with COLCOVID, a test of colchicine in patients hospitalized for suspected SARS-CoV-2 infection and in acute respiratory distress.

The 1,279 participants in Argentina were randomly assigned to receive or not receive the potent anti-inflammatory agent on top of antivirals and other standard management and followed for death or new need for mechanical ventilation. A successful outcome would contrast with the RECOVERY trial, which terminated a colchicine group of patients hospitalized with COVID-19 because of a lack of efficacy earlier this year.

COLCOVID is to be followed by the MICHELLE trial of rivaroxaban (Xarelto, Bayer/Janssen) prophylaxis, compared with no preventive oral anticoagulant, in 320 patients who, when hospitalized with COVID-19, had been on parenteral anticoagulants because of an elevated risk for venous thromboembolism. The trial, conducted in Brazil, called for postdischarge rivaroxaban at a once-daily dosage of 10 mg for about 1 month.

The session also includes a presentation called “Insights into the Effects of the COVID-19 Pandemic: Comprehensive Analysis from the GUIDE-HF Trial,” the primary outcomes of which will be reported on the first day of the Congress.

Following is a presentation on the PREPARE-IT study of icosapent ethyl (Vascepa, Amarin), given at high dosages intended to be anti-inflammatory, compared with placebo, in an estimated 4,000 adults. The trial has two groups: A prevention group of adults living and circulating in the community; and a treatment group of patients aged at least 40 years with confirmed symptomatic SARS-CoV-2 infection for whom the need for hospitalization isn’t clear.
 

Monday, Aug. 30

The final day of the Congress features a trial called Influenza Vaccination after Myocardial Infarction (IAMI), which has tested the secondary preventive effect of influenza vaccination by randomly assigning 2,571 patients to receive a standard vaccine or a saline placebo injection on one occasion.

Entry to the international trial called for a diagnosis of MI with or without ST-segment elevation, or stable CAD and age at least 75 years with other risk factors. The patients were followed for death, MI, stent thrombosis, and a slew of secondary endpoints over 12 months.

Monday offerings continue later in a time block leading off with the STEP trial, which has randomly assigned an estimated 8,000 patients at 40 centers in China who are 60 to 80 years of age with a systolic blood pressure of 140 to <190 mm Hg to be on standard guideline-based therapy or an intensive drug-management strategy.

The systolic BP goals are 130 to <150 mm Hg for standard care and 110 to <130 mm Hg for the intensive regimen. The composite primary endpoint includes death and clinical events related to acute coronary syndromes, HF, revascularization, and stroke.

Following on heels of STEP, the Amulet IDE trial – the first major randomized comparison of two transcatheter LAA closure devices – entered 1,878 patients with nonvalvular AFib who were considered high-risk for bleeding and stroke or systemic embolism.

They were randomly assigned in the noninferiority trial to receive either the AMPLATZER Amulet (Abbott Medical Devices) or the WATCHMAN (Boston Scientific) closure devices and were followed for safety and efficacy for up to 5 years.

Both LAA closure devices, intended to make patients with AFib less reliant on oral anticoagulation, are now available on both sides of the Atlantic – as well as many other countries – after the Amulet’s United States market approval on Aug. 16, based largely on the Amulet IDE trial.

Rounding out the final Hot Line set is one of the latest efforts to show the efficacy and safety of a very short DAPT period after coronary stenting in patients with acute coronary syndromes, the STOPDAPT-2 ACS trial.

The study assigned 3,008 patients in Japan to receive aspirin and clopidogrel for either 1 month or 1 year after implantation with an everolimus-eluting cobalt-chromium stent and followed them for up to 5 years for a composite of MI, CV death, stent thrombosis, stroke, and bleeding.

The trial follows the published STOPDAPT-2 trial that showed superiority for the 1-month DAPT regimen in a predominantly stable-CAD population treated with the same kind of stent.
 

Program structure and format

A total of 15 online channels are to be available in the morning, European time, their schedules running in parallel. Presentations often are prerecorded, but also include live sessions at 8:00 a.m. Central time and 12 p.m. CET (2:00 a.m. and 6:00 a.m. Eastern time) to liven up the channel offerings, Dr. Windecker observed, and to make them more immediate and potentially interactive.

Many of the parallel channels are devoted throughout the Congress to particular silos of cardiology; for example, arrhythmias and device therapy is on channel 3; CAD and acute care is on 5; HF is on 6; and preventive cardiology is on 9.

Other channels swing across different topics from day to day, such as channel 1, which covers COVID-19 topics on the first and third day of the meeting, “advances in science” on day 2, and “digital health, public health, health economics” on day 4.

The focus each day, starting at 2:00 p.m. CET (8:00 a.m. ET) and continuing into the evening in Europe, shifts over to the Prime Time live program, which features the Hot Line and guideline presentations and many of the live abstract presentations.

Dr. Kosiborod, not a researcher with the EMPEROR trials, is chair of the Dapagliflozin in Preserved Ejection Fraction Heart Failure ( PRESERVED-HF ) trial, which is scheduled for presentation at the September 2021 Heart Failure Society of American meeting.

A version of this article first appeared on Medscape.com.

There will be so much more to the annual congress of the European Society of Cardiology, which begins Aug. 27 with an all-virtual format, than detailed primary results of EMPEROR-Preserved, a trial that could mark a turning point for heart failure (HF) medical therapy.

Also among the featured Hot Line and Late-Breaking Science sessions are – along with many other studies – explorations of arrhythmia management (ablation or guided by loop recorder); secondary prevention, including by vaccination; oral anticoagulation, notably after transcatheter valve procedures; and colchicine or thrombosis prophylaxis in hospitalized patients with COVID-19.

There will even be a head-to-head comparison of two long-familiar left atrial appendage (LAA) occluders, and a population-based, randomized trial of sodium restriction through wide-scale use of a potassium-based salt substitute.

The congress will also introduce four guideline documents at sessions throughout the Congress, one on each day. They cover new and modified recommendations for heart failure; pacing, including cardiac resynchronization therapy (CRT); cardiovascular (CV) disease prevention; and, with cosponsorship from the European Association for Cardio-Thoracic Surgery, valvular heart disease.
 

The virtues of virtual

That next year’s Congress is slated for Aug. 27-30 in Barcelona should be welcome news for anyone whose “what if” curiosity about all-virtual conferences has already been satisfied. But with experience comes wisdom, as the medical societies have learned that online scientific meetings have some winning qualities that may be worth keeping, as least for a while.

“I think there is no doubt that the digital format will continue, for several reasons. One is that this pandemic is not over,” ESC Congress program committee chair Stephan Windecker, MD, Bern (Switzerland) University Hospital, , told this news organization. “As long as it is not over, the digital format is here to stay.”

But it also appears that people who haven’t been able to attend the congress in person are keen to log in and engage online, Dr. Windecker said. The 2020 all-virtual conference drew a much younger pool of registrants, on average, than did the live conferences before the pandemic.

“I think that’s an indication of people that may be in training, in early stages of their career, or they don’t have the support from departments or from their practice, or other financial means.” But they are able to participate via computer, tablet, or smartphone, he said.

“Another advantage is that the recorded content can be replayed at the convenience of whoever wants to consume it at a later point in time,” he added. “Those are just some examples why the digital format is likely to stay,” on its own or in a new age of hybrid meetings.  
 

New and updated guidelines

Leading off the guideline series is the document on diagnosis and treatment of acute and chronic HF, which leveraged the past few busy years of HF clinical trials to arrive at a number of new recommendations and strengthened level-of-evidence ratings. It covers both drug and device therapy of HF with reduced ejection fraction (HFrEF) and acute decompensated HF, and tweaks and further enshrines the concept of HF with mildly reduced ejection fraction (HFmrEF).

Several updated recommendations for both long-used and novel medications, notably the sodium-glucose cotransporter 2 inhibitors, will be included because of the recently appreciated evidence-based impact in HFrEF, Dr. Windecker noted.

“I think it will be particularly interesting to look for the SGLT2 inhibitors as not a completely new class of drugs, but certainly one where there has been a lot of new evidence, to look at how those drugs will be integrated in the overall care pathway.”

A top-line preview of the new HF guideline limited to drug therapy, presented at July’s Heart Failure Association of the European Society of Cardiology (ESC-HFA), provided a simple answer to a common question in the new, bountiful age of HFrEF medications: Which meds, initiated in what order?

As it happens, the new recommendation for first-line HFrEF drug therapy is not a silver bullet, but a shotgun – prompt initiation of at least four meds, one from each of four drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors. Each class, as described in the document, is to be started as soon as safely feasible, in a sequence deemed appropriate for each individual patient.
 

Spotlight on EMPEROR-Preserved

The world already knows that the trial, which tested the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) on top of standard therapy, “met” its primary endpoint in almost 6,000 patients with HF with preserved ejection fraction (HFpEF), who included some with HFmrEF by more contemporary definitions.

That means patients in EMPEROR-Preserved assigned to take empagliflozin showed significantly fewer events that made up the study’s primary endpoint, a composite of CV death or HF hospitalization. It appears to be the first clearly significant overall medical therapy benefit for a clinical primary endpoint in a major randomized HFpEF drug trial.

And that, pending fuller presentation of trial results at the Congress on Aug. 27, could be a huge deal for the half of HF patients with left ventricular ejection fractions (LVEF) higher than the HFrEF range.

Those early top-line results weren’t a decisive bombshell for a field now filled with hope for a practice-changing empagliflozin outcome in EMPEROR-Preserved, which isn’t a certainty. They were more like the “boom” of a mortar launching a rocket of fireworks that may explode into a chrysanthemum or green comet or, sometimes, turn out to be no more than a dud. The promise of the early cursory results critically depends on further details.

“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades,” Mikhail N. Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said.

“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don’t know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalizations and cardiovascular death, or only one of the two.”

For example: “If we see an impressive benefit for reduction of hospitalizations, but not a significant reduction in death, that would still be a huge advance. That’s because, to date, we don’t have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalization or improvement in symptoms, function, or quality of life,” observed Dr. Kosiborod, who wasn’t part of EMPEROR-Preserved.

There have been “suggestions” from HFrEF trials that empagliflozin and dapagliflozin (Farxiga, AstraZeneca) “have very comparable effects on at least the endpoint of cardiovascular death or hospitalization for heart failure,” he said. “So, my expectation would be that whatever is observed in EMPEROR-Preserved is likely a class effect, as well.”

Following EMPEROR-Preserved on the agenda is EMPEROR-Pooled, a patient-level combined analysis of the EMPEROR series of trials that spans the range of HF, regardless of ejection fraction or diabetes status, primarily exploring the effects of empagliflozin on renal function.
 

Other offerings, Friday, Aug. 27

Scheduled immediately after EMPEROR-Preserved is a presentation on the SMART-MI trial, which should clarify whether management guided by continuous ambulatory monitoring is effective in patients considered at especially high arrhythmic risk. Entry called for recent myocardial infarction and an LVEF of 36%-50% with evidence of cardiac autonomic dysfunction.

The trial randomly assigned 400 such patients to be or not be implanted with a Reveal LINQ (Medtronic) loop recorder and followed them for up to 18 months, primarily for detection of potentially serious arrhythmic events. Endpoints that involved mortality, hospitalization or other clinical events were secondary.

In a time slot preceding both SMART-MI and EMPEROR-Preserved, the GUIDE-HF trial is following a projected 3,600 patients with HF implanted with a CardioMEMS HF System (Abbott) pulmonary artery (PA) pressure sensor to explore the its value for guiding management.

The trial’s three cohorts, followed for at least 12 months, include randomized sensor-monitored and control groups of patients with New York Heart Association class 2-4 symptoms, as well as a third observational set of patients in NYHA class 3. That’s the indication for which the CardioMEMS monitor gained approval in the United States in 2014 based on the 2011 CHAMPION trial, and which fared just as well in the 2017 CHAMPION Post-Approval Study.

The Friday Hot Lines also include Dal-GenE, which has entered about 6,000 patients with recent MI to test the once-abandoned cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DalCor) for any secondary-prevention benefits when used selectively. The trial’s hook: All its patients are confirmed to have the AA genotype of the rs1967309 variant in the ADCY9 gene, which has been associated with a pronounced clinical response to CETP inhibition.

Saturday, Aug. 28

The direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in patients with nonvalvular atrial fibrillation (AFib). But whether DOACs are similarly preferable in the growing world population of people who have undergone transcatheter aortic valve replacement (TAVR or TAVI), an issue explored with variable results in the ATLANTIS and GALILEO trials, is far from settled.

The ENVISAGE-TAVI AF trial explored the question for the factor X inhibitor edoxaban (Savaysa, Lixiana, Daiichi-Sankyo) in 1,400 patients with AFib and a transfemoral TAVR in the previous 5 days, who were randomly assigned to the DOAC or standard management along with discretionary antiplatelet therapy. They’ve been followed for up to 3 years for a composite endpoint of clinical events – including death, MI, and stroke – and for major bleeding.

The day will also feature MASTER DAPT, a comparison of two dual-antiplatelet therapy (DAPT) regimens in an estimated 4,300 patients considered to be high-risk for bleeding who had received the sirolimus-eluting Ultimaster (Terumo) coronary stent, which has a bioresorbable polymer coating.

Investigators have randomly assigned patients to receive either very-short-duration DAPT, for about a month after stenting, followed by a P2Y12 inhibitor alone for up to a year after the procedure; or a more conventional regimen of a P2Y12 inhibitor for 6-12 months with aspirin maintained for a total of 12 months.

Later that day, investigators from the FIGARO-DKD trial will present their results based on 7,437 patients with type 2 diabetes and chronic kidney disease (CKD), a much fuller version than the top-line findings announced by sponsor Bayer 3 months ago.

Those top-line results suggested that patients assigned to receive the nonsteroidal nonselective mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) on top of standard care benefited with a drop in risk for the primary endpoint of CV death or nonfatal CV events.

Finerenone was recently approved in the United States for treating patients with both type 2 diabetes and CKD based on the published FIDELIO-DKD trial, which had seen less CKD progression and fewer CV events in such patients who took the novel MRA.

Although similar in design to FIGARO-DKD, FIDELIO-DKD had entered fewer patients with early-stage diabetic kidney disease (DKD). That led researchers to pool the two trials’ populations to create a cohort that spans the spectrum of DKD severity. An analysis of the pooled cohort, dubbed FIDELITY, is on the schedule after FIGARO-DKD.

After FIDELITY is the prospective APAF-CRT trial that is following a projected 1,830 patients with permanent, symptomatic AFib and a recent hospitalization for AFib or HF and who were not good candidates for standard ablation. They were assigned to receive either atrioventricular junctional ablation followed by CRT, with or without a defibrillation, on top of optimal meds – a so-called “ablate-and-pace” strategy – or an implantable cardioverter defibrillator with rate-control drug therapy.

The new analysis represents the trial’s second phase in which mortality was followed for 4 years as the primary endpoint, in contrast to the previously reported initial phase that followed the first 102 patients for 2 years for the composite primary endpoint of death, worsening HF, and HF hospitalization. The first phase had halted enrollment before reaching its planned target of 280 patients after an interim analysis showed a significant benefit for ablate and pace. 

Next up: DECAAF 2, a randomized assessment of whether catheter ablation for AFib guided by delayed gadolinium enhancement on MRI, a proxy for scar tissue, can be more effective than standard AFib ablation by pulmonary vein isolation alone. An estimated 900 patients with persistent AFib who had never before undergone ablation for the arrhythmia were randomly assigned to one strategy or the other and followed for AFib recurrence over 18 months.
 

Sunday, Aug. 29

The TOMAHAWK trial aimed to clarify the optimal timing of invasive coronary angiography for resuscitated patients with non–ST-segment elevation out-of-hospital cardiac arrest, a broad population in a setting for which there is little randomized-trial guidance. Investigators randomly assigned 558 such patients to undergo immediate invasive angiography or to direct intensive care unit admission for initial standard care with discretionary delayed angiography. Patients were followed for all-cause mortality, with other clinical events and neurologic outcomes as secondary endpoints.

Next on the schedule, the RIPCORD-2 trial randomly assigned 1,100 patients with stable known or suspected coronary artery disease (CAD) to undergo conventional angiography alone or with added direct pressure-wire measurement of fractional flow reserve to guide management decisions. Primary outcomes include health care costs and patient-reported quality of life at 1 year.

Slated for later that day, the Asymptomatic Carotid Surgery Trial-2 (ACST-2) has entered an estimated 3600 patients with a substantial carotid artery narrowing not associated with symptoms but for which either carotid endarterectomy (CEA) or carotid artery stenting (CAS) was considered anatomically feasible. There also must have been “substantial uncertainty” regarding the optimal procedure choice.

The trial, conducted in 40 countries primarily in Europe and North America and launched in 2008, randomly assigned the patients to undergo either CEA or CAS, in both cases with appropriate medical therapy, and followed them for periprocedural events and up to 10 years for strokes and stroke-related events.

The LOOP study, which is to directly follow ACST-2, has explored whether screening for AFib using the Medtronic Reveal LINQ monitor in older patients with non-AFib stroke risk factors – with oral anticoagulation prescribed for those who test positive – can lower their risk for stroke or systemic embolism. It randomly assigned 6,000 such patients to care guided by the loop recorder or to standard care.

On a somewhat larger scale, the Salt Substitute and Stroke Study (SSaSS) randomly assigned a total of 20,996 people in about 600 villages across northern China and Tibet to sodium-restriction intervention and control groups by village. All participants had a history of stroke or were aged at least 60 years with uncontrolled hypertension.

As described by the trial’s online portal, participants in villages assigned to the intervention group were given a supply of a low-sodium, potassium-supplementing salt substitute to replace their own salt supplies, along with education on the health benefits of sodium restriction. Participants in control villages continued their normal diets and, at the trial’s beginning, received “advice to reduce their salt intake.” All were required to own a telephone.

Clinical events, including strokes and hospitalizations throughout a 5-year follow-up, were tracked by phone calls made to all participants every 6 months and were documented at follow-up home visits.

Sunday is also to feature a Late-Breaking Trials session with a focus on COVID-19, which leads off with COLCOVID, a test of colchicine in patients hospitalized for suspected SARS-CoV-2 infection and in acute respiratory distress.

The 1,279 participants in Argentina were randomly assigned to receive or not receive the potent anti-inflammatory agent on top of antivirals and other standard management and followed for death or new need for mechanical ventilation. A successful outcome would contrast with the RECOVERY trial, which terminated a colchicine group of patients hospitalized with COVID-19 because of a lack of efficacy earlier this year.

COLCOVID is to be followed by the MICHELLE trial of rivaroxaban (Xarelto, Bayer/Janssen) prophylaxis, compared with no preventive oral anticoagulant, in 320 patients who, when hospitalized with COVID-19, had been on parenteral anticoagulants because of an elevated risk for venous thromboembolism. The trial, conducted in Brazil, called for postdischarge rivaroxaban at a once-daily dosage of 10 mg for about 1 month.

The session also includes a presentation called “Insights into the Effects of the COVID-19 Pandemic: Comprehensive Analysis from the GUIDE-HF Trial,” the primary outcomes of which will be reported on the first day of the Congress.

Following is a presentation on the PREPARE-IT study of icosapent ethyl (Vascepa, Amarin), given at high dosages intended to be anti-inflammatory, compared with placebo, in an estimated 4,000 adults. The trial has two groups: A prevention group of adults living and circulating in the community; and a treatment group of patients aged at least 40 years with confirmed symptomatic SARS-CoV-2 infection for whom the need for hospitalization isn’t clear.
 

Monday, Aug. 30

The final day of the Congress features a trial called Influenza Vaccination after Myocardial Infarction (IAMI), which has tested the secondary preventive effect of influenza vaccination by randomly assigning 2,571 patients to receive a standard vaccine or a saline placebo injection on one occasion.

Entry to the international trial called for a diagnosis of MI with or without ST-segment elevation, or stable CAD and age at least 75 years with other risk factors. The patients were followed for death, MI, stent thrombosis, and a slew of secondary endpoints over 12 months.

Monday offerings continue later in a time block leading off with the STEP trial, which has randomly assigned an estimated 8,000 patients at 40 centers in China who are 60 to 80 years of age with a systolic blood pressure of 140 to <190 mm Hg to be on standard guideline-based therapy or an intensive drug-management strategy.

The systolic BP goals are 130 to <150 mm Hg for standard care and 110 to <130 mm Hg for the intensive regimen. The composite primary endpoint includes death and clinical events related to acute coronary syndromes, HF, revascularization, and stroke.

Following on heels of STEP, the Amulet IDE trial – the first major randomized comparison of two transcatheter LAA closure devices – entered 1,878 patients with nonvalvular AFib who were considered high-risk for bleeding and stroke or systemic embolism.

They were randomly assigned in the noninferiority trial to receive either the AMPLATZER Amulet (Abbott Medical Devices) or the WATCHMAN (Boston Scientific) closure devices and were followed for safety and efficacy for up to 5 years.

Both LAA closure devices, intended to make patients with AFib less reliant on oral anticoagulation, are now available on both sides of the Atlantic – as well as many other countries – after the Amulet’s United States market approval on Aug. 16, based largely on the Amulet IDE trial.

Rounding out the final Hot Line set is one of the latest efforts to show the efficacy and safety of a very short DAPT period after coronary stenting in patients with acute coronary syndromes, the STOPDAPT-2 ACS trial.

The study assigned 3,008 patients in Japan to receive aspirin and clopidogrel for either 1 month or 1 year after implantation with an everolimus-eluting cobalt-chromium stent and followed them for up to 5 years for a composite of MI, CV death, stent thrombosis, stroke, and bleeding.

The trial follows the published STOPDAPT-2 trial that showed superiority for the 1-month DAPT regimen in a predominantly stable-CAD population treated with the same kind of stent.
 

Program structure and format

A total of 15 online channels are to be available in the morning, European time, their schedules running in parallel. Presentations often are prerecorded, but also include live sessions at 8:00 a.m. Central time and 12 p.m. CET (2:00 a.m. and 6:00 a.m. Eastern time) to liven up the channel offerings, Dr. Windecker observed, and to make them more immediate and potentially interactive.

Many of the parallel channels are devoted throughout the Congress to particular silos of cardiology; for example, arrhythmias and device therapy is on channel 3; CAD and acute care is on 5; HF is on 6; and preventive cardiology is on 9.

Other channels swing across different topics from day to day, such as channel 1, which covers COVID-19 topics on the first and third day of the meeting, “advances in science” on day 2, and “digital health, public health, health economics” on day 4.

The focus each day, starting at 2:00 p.m. CET (8:00 a.m. ET) and continuing into the evening in Europe, shifts over to the Prime Time live program, which features the Hot Line and guideline presentations and many of the live abstract presentations.

Dr. Kosiborod, not a researcher with the EMPEROR trials, is chair of the Dapagliflozin in Preserved Ejection Fraction Heart Failure ( PRESERVED-HF ) trial, which is scheduled for presentation at the September 2021 Heart Failure Society of American meeting.

A version of this article first appeared on Medscape.com.

There will be so much more to the annual congress of the European Society of Cardiology, which begins Aug. 27 with an all-virtual format, than detailed primary results of EMPEROR-Preserved, a trial that could mark a turning point for heart failure (HF) medical therapy.

Also among the featured Hot Line and Late-Breaking Science sessions are – along with many other studies – explorations of arrhythmia management (ablation or guided by loop recorder); secondary prevention, including by vaccination; oral anticoagulation, notably after transcatheter valve procedures; and colchicine or thrombosis prophylaxis in hospitalized patients with COVID-19.

There will even be a head-to-head comparison of two long-familiar left atrial appendage (LAA) occluders, and a population-based, randomized trial of sodium restriction through wide-scale use of a potassium-based salt substitute.

The congress will also introduce four guideline documents at sessions throughout the Congress, one on each day. They cover new and modified recommendations for heart failure; pacing, including cardiac resynchronization therapy (CRT); cardiovascular (CV) disease prevention; and, with cosponsorship from the European Association for Cardio-Thoracic Surgery, valvular heart disease.
 

The virtues of virtual

That next year’s Congress is slated for Aug. 27-30 in Barcelona should be welcome news for anyone whose “what if” curiosity about all-virtual conferences has already been satisfied. But with experience comes wisdom, as the medical societies have learned that online scientific meetings have some winning qualities that may be worth keeping, as least for a while.

“I think there is no doubt that the digital format will continue, for several reasons. One is that this pandemic is not over,” ESC Congress program committee chair Stephan Windecker, MD, Bern (Switzerland) University Hospital, , told this news organization. “As long as it is not over, the digital format is here to stay.”

But it also appears that people who haven’t been able to attend the congress in person are keen to log in and engage online, Dr. Windecker said. The 2020 all-virtual conference drew a much younger pool of registrants, on average, than did the live conferences before the pandemic.

“I think that’s an indication of people that may be in training, in early stages of their career, or they don’t have the support from departments or from their practice, or other financial means.” But they are able to participate via computer, tablet, or smartphone, he said.

“Another advantage is that the recorded content can be replayed at the convenience of whoever wants to consume it at a later point in time,” he added. “Those are just some examples why the digital format is likely to stay,” on its own or in a new age of hybrid meetings.  
 

New and updated guidelines

Leading off the guideline series is the document on diagnosis and treatment of acute and chronic HF, which leveraged the past few busy years of HF clinical trials to arrive at a number of new recommendations and strengthened level-of-evidence ratings. It covers both drug and device therapy of HF with reduced ejection fraction (HFrEF) and acute decompensated HF, and tweaks and further enshrines the concept of HF with mildly reduced ejection fraction (HFmrEF).

Several updated recommendations for both long-used and novel medications, notably the sodium-glucose cotransporter 2 inhibitors, will be included because of the recently appreciated evidence-based impact in HFrEF, Dr. Windecker noted.

“I think it will be particularly interesting to look for the SGLT2 inhibitors as not a completely new class of drugs, but certainly one where there has been a lot of new evidence, to look at how those drugs will be integrated in the overall care pathway.”

A top-line preview of the new HF guideline limited to drug therapy, presented at July’s Heart Failure Association of the European Society of Cardiology (ESC-HFA), provided a simple answer to a common question in the new, bountiful age of HFrEF medications: Which meds, initiated in what order?

As it happens, the new recommendation for first-line HFrEF drug therapy is not a silver bullet, but a shotgun – prompt initiation of at least four meds, one from each of four drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors. Each class, as described in the document, is to be started as soon as safely feasible, in a sequence deemed appropriate for each individual patient.
 

Spotlight on EMPEROR-Preserved

The world already knows that the trial, which tested the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) on top of standard therapy, “met” its primary endpoint in almost 6,000 patients with HF with preserved ejection fraction (HFpEF), who included some with HFmrEF by more contemporary definitions.

That means patients in EMPEROR-Preserved assigned to take empagliflozin showed significantly fewer events that made up the study’s primary endpoint, a composite of CV death or HF hospitalization. It appears to be the first clearly significant overall medical therapy benefit for a clinical primary endpoint in a major randomized HFpEF drug trial.

And that, pending fuller presentation of trial results at the Congress on Aug. 27, could be a huge deal for the half of HF patients with left ventricular ejection fractions (LVEF) higher than the HFrEF range.

Those early top-line results weren’t a decisive bombshell for a field now filled with hope for a practice-changing empagliflozin outcome in EMPEROR-Preserved, which isn’t a certainty. They were more like the “boom” of a mortar launching a rocket of fireworks that may explode into a chrysanthemum or green comet or, sometimes, turn out to be no more than a dud. The promise of the early cursory results critically depends on further details.

“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades,” Mikhail N. Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said.

“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don’t know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalizations and cardiovascular death, or only one of the two.”

For example: “If we see an impressive benefit for reduction of hospitalizations, but not a significant reduction in death, that would still be a huge advance. That’s because, to date, we don’t have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalization or improvement in symptoms, function, or quality of life,” observed Dr. Kosiborod, who wasn’t part of EMPEROR-Preserved.

There have been “suggestions” from HFrEF trials that empagliflozin and dapagliflozin (Farxiga, AstraZeneca) “have very comparable effects on at least the endpoint of cardiovascular death or hospitalization for heart failure,” he said. “So, my expectation would be that whatever is observed in EMPEROR-Preserved is likely a class effect, as well.”

Following EMPEROR-Preserved on the agenda is EMPEROR-Pooled, a patient-level combined analysis of the EMPEROR series of trials that spans the range of HF, regardless of ejection fraction or diabetes status, primarily exploring the effects of empagliflozin on renal function.
 

Other offerings, Friday, Aug. 27

Scheduled immediately after EMPEROR-Preserved is a presentation on the SMART-MI trial, which should clarify whether management guided by continuous ambulatory monitoring is effective in patients considered at especially high arrhythmic risk. Entry called for recent myocardial infarction and an LVEF of 36%-50% with evidence of cardiac autonomic dysfunction.

The trial randomly assigned 400 such patients to be or not be implanted with a Reveal LINQ (Medtronic) loop recorder and followed them for up to 18 months, primarily for detection of potentially serious arrhythmic events. Endpoints that involved mortality, hospitalization or other clinical events were secondary.

In a time slot preceding both SMART-MI and EMPEROR-Preserved, the GUIDE-HF trial is following a projected 3,600 patients with HF implanted with a CardioMEMS HF System (Abbott) pulmonary artery (PA) pressure sensor to explore the its value for guiding management.

The trial’s three cohorts, followed for at least 12 months, include randomized sensor-monitored and control groups of patients with New York Heart Association class 2-4 symptoms, as well as a third observational set of patients in NYHA class 3. That’s the indication for which the CardioMEMS monitor gained approval in the United States in 2014 based on the 2011 CHAMPION trial, and which fared just as well in the 2017 CHAMPION Post-Approval Study.

The Friday Hot Lines also include Dal-GenE, which has entered about 6,000 patients with recent MI to test the once-abandoned cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DalCor) for any secondary-prevention benefits when used selectively. The trial’s hook: All its patients are confirmed to have the AA genotype of the rs1967309 variant in the ADCY9 gene, which has been associated with a pronounced clinical response to CETP inhibition.

Saturday, Aug. 28

The direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in patients with nonvalvular atrial fibrillation (AFib). But whether DOACs are similarly preferable in the growing world population of people who have undergone transcatheter aortic valve replacement (TAVR or TAVI), an issue explored with variable results in the ATLANTIS and GALILEO trials, is far from settled.

The ENVISAGE-TAVI AF trial explored the question for the factor X inhibitor edoxaban (Savaysa, Lixiana, Daiichi-Sankyo) in 1,400 patients with AFib and a transfemoral TAVR in the previous 5 days, who were randomly assigned to the DOAC or standard management along with discretionary antiplatelet therapy. They’ve been followed for up to 3 years for a composite endpoint of clinical events – including death, MI, and stroke – and for major bleeding.

The day will also feature MASTER DAPT, a comparison of two dual-antiplatelet therapy (DAPT) regimens in an estimated 4,300 patients considered to be high-risk for bleeding who had received the sirolimus-eluting Ultimaster (Terumo) coronary stent, which has a bioresorbable polymer coating.

Investigators have randomly assigned patients to receive either very-short-duration DAPT, for about a month after stenting, followed by a P2Y12 inhibitor alone for up to a year after the procedure; or a more conventional regimen of a P2Y12 inhibitor for 6-12 months with aspirin maintained for a total of 12 months.

Later that day, investigators from the FIGARO-DKD trial will present their results based on 7,437 patients with type 2 diabetes and chronic kidney disease (CKD), a much fuller version than the top-line findings announced by sponsor Bayer 3 months ago.

Those top-line results suggested that patients assigned to receive the nonsteroidal nonselective mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) on top of standard care benefited with a drop in risk for the primary endpoint of CV death or nonfatal CV events.

Finerenone was recently approved in the United States for treating patients with both type 2 diabetes and CKD based on the published FIDELIO-DKD trial, which had seen less CKD progression and fewer CV events in such patients who took the novel MRA.

Although similar in design to FIGARO-DKD, FIDELIO-DKD had entered fewer patients with early-stage diabetic kidney disease (DKD). That led researchers to pool the two trials’ populations to create a cohort that spans the spectrum of DKD severity. An analysis of the pooled cohort, dubbed FIDELITY, is on the schedule after FIGARO-DKD.

After FIDELITY is the prospective APAF-CRT trial that is following a projected 1,830 patients with permanent, symptomatic AFib and a recent hospitalization for AFib or HF and who were not good candidates for standard ablation. They were assigned to receive either atrioventricular junctional ablation followed by CRT, with or without a defibrillation, on top of optimal meds – a so-called “ablate-and-pace” strategy – or an implantable cardioverter defibrillator with rate-control drug therapy.

The new analysis represents the trial’s second phase in which mortality was followed for 4 years as the primary endpoint, in contrast to the previously reported initial phase that followed the first 102 patients for 2 years for the composite primary endpoint of death, worsening HF, and HF hospitalization. The first phase had halted enrollment before reaching its planned target of 280 patients after an interim analysis showed a significant benefit for ablate and pace. 

Next up: DECAAF 2, a randomized assessment of whether catheter ablation for AFib guided by delayed gadolinium enhancement on MRI, a proxy for scar tissue, can be more effective than standard AFib ablation by pulmonary vein isolation alone. An estimated 900 patients with persistent AFib who had never before undergone ablation for the arrhythmia were randomly assigned to one strategy or the other and followed for AFib recurrence over 18 months.
 

Sunday, Aug. 29

The TOMAHAWK trial aimed to clarify the optimal timing of invasive coronary angiography for resuscitated patients with non–ST-segment elevation out-of-hospital cardiac arrest, a broad population in a setting for which there is little randomized-trial guidance. Investigators randomly assigned 558 such patients to undergo immediate invasive angiography or to direct intensive care unit admission for initial standard care with discretionary delayed angiography. Patients were followed for all-cause mortality, with other clinical events and neurologic outcomes as secondary endpoints.

Next on the schedule, the RIPCORD-2 trial randomly assigned 1,100 patients with stable known or suspected coronary artery disease (CAD) to undergo conventional angiography alone or with added direct pressure-wire measurement of fractional flow reserve to guide management decisions. Primary outcomes include health care costs and patient-reported quality of life at 1 year.

Slated for later that day, the Asymptomatic Carotid Surgery Trial-2 (ACST-2) has entered an estimated 3600 patients with a substantial carotid artery narrowing not associated with symptoms but for which either carotid endarterectomy (CEA) or carotid artery stenting (CAS) was considered anatomically feasible. There also must have been “substantial uncertainty” regarding the optimal procedure choice.

The trial, conducted in 40 countries primarily in Europe and North America and launched in 2008, randomly assigned the patients to undergo either CEA or CAS, in both cases with appropriate medical therapy, and followed them for periprocedural events and up to 10 years for strokes and stroke-related events.

The LOOP study, which is to directly follow ACST-2, has explored whether screening for AFib using the Medtronic Reveal LINQ monitor in older patients with non-AFib stroke risk factors – with oral anticoagulation prescribed for those who test positive – can lower their risk for stroke or systemic embolism. It randomly assigned 6,000 such patients to care guided by the loop recorder or to standard care.

On a somewhat larger scale, the Salt Substitute and Stroke Study (SSaSS) randomly assigned a total of 20,996 people in about 600 villages across northern China and Tibet to sodium-restriction intervention and control groups by village. All participants had a history of stroke or were aged at least 60 years with uncontrolled hypertension.

As described by the trial’s online portal, participants in villages assigned to the intervention group were given a supply of a low-sodium, potassium-supplementing salt substitute to replace their own salt supplies, along with education on the health benefits of sodium restriction. Participants in control villages continued their normal diets and, at the trial’s beginning, received “advice to reduce their salt intake.” All were required to own a telephone.

Clinical events, including strokes and hospitalizations throughout a 5-year follow-up, were tracked by phone calls made to all participants every 6 months and were documented at follow-up home visits.

Sunday is also to feature a Late-Breaking Trials session with a focus on COVID-19, which leads off with COLCOVID, a test of colchicine in patients hospitalized for suspected SARS-CoV-2 infection and in acute respiratory distress.

The 1,279 participants in Argentina were randomly assigned to receive or not receive the potent anti-inflammatory agent on top of antivirals and other standard management and followed for death or new need for mechanical ventilation. A successful outcome would contrast with the RECOVERY trial, which terminated a colchicine group of patients hospitalized with COVID-19 because of a lack of efficacy earlier this year.

COLCOVID is to be followed by the MICHELLE trial of rivaroxaban (Xarelto, Bayer/Janssen) prophylaxis, compared with no preventive oral anticoagulant, in 320 patients who, when hospitalized with COVID-19, had been on parenteral anticoagulants because of an elevated risk for venous thromboembolism. The trial, conducted in Brazil, called for postdischarge rivaroxaban at a once-daily dosage of 10 mg for about 1 month.

The session also includes a presentation called “Insights into the Effects of the COVID-19 Pandemic: Comprehensive Analysis from the GUIDE-HF Trial,” the primary outcomes of which will be reported on the first day of the Congress.

Following is a presentation on the PREPARE-IT study of icosapent ethyl (Vascepa, Amarin), given at high dosages intended to be anti-inflammatory, compared with placebo, in an estimated 4,000 adults. The trial has two groups: A prevention group of adults living and circulating in the community; and a treatment group of patients aged at least 40 years with confirmed symptomatic SARS-CoV-2 infection for whom the need for hospitalization isn’t clear.
 

Monday, Aug. 30

The final day of the Congress features a trial called Influenza Vaccination after Myocardial Infarction (IAMI), which has tested the secondary preventive effect of influenza vaccination by randomly assigning 2,571 patients to receive a standard vaccine or a saline placebo injection on one occasion.

Entry to the international trial called for a diagnosis of MI with or without ST-segment elevation, or stable CAD and age at least 75 years with other risk factors. The patients were followed for death, MI, stent thrombosis, and a slew of secondary endpoints over 12 months.

Monday offerings continue later in a time block leading off with the STEP trial, which has randomly assigned an estimated 8,000 patients at 40 centers in China who are 60 to 80 years of age with a systolic blood pressure of 140 to <190 mm Hg to be on standard guideline-based therapy or an intensive drug-management strategy.

The systolic BP goals are 130 to <150 mm Hg for standard care and 110 to <130 mm Hg for the intensive regimen. The composite primary endpoint includes death and clinical events related to acute coronary syndromes, HF, revascularization, and stroke.

Following on heels of STEP, the Amulet IDE trial – the first major randomized comparison of two transcatheter LAA closure devices – entered 1,878 patients with nonvalvular AFib who were considered high-risk for bleeding and stroke or systemic embolism.

They were randomly assigned in the noninferiority trial to receive either the AMPLATZER Amulet (Abbott Medical Devices) or the WATCHMAN (Boston Scientific) closure devices and were followed for safety and efficacy for up to 5 years.

Both LAA closure devices, intended to make patients with AFib less reliant on oral anticoagulation, are now available on both sides of the Atlantic – as well as many other countries – after the Amulet’s United States market approval on Aug. 16, based largely on the Amulet IDE trial.

Rounding out the final Hot Line set is one of the latest efforts to show the efficacy and safety of a very short DAPT period after coronary stenting in patients with acute coronary syndromes, the STOPDAPT-2 ACS trial.

The study assigned 3,008 patients in Japan to receive aspirin and clopidogrel for either 1 month or 1 year after implantation with an everolimus-eluting cobalt-chromium stent and followed them for up to 5 years for a composite of MI, CV death, stent thrombosis, stroke, and bleeding.

The trial follows the published STOPDAPT-2 trial that showed superiority for the 1-month DAPT regimen in a predominantly stable-CAD population treated with the same kind of stent.
 

Program structure and format

A total of 15 online channels are to be available in the morning, European time, their schedules running in parallel. Presentations often are prerecorded, but also include live sessions at 8:00 a.m. Central time and 12 p.m. CET (2:00 a.m. and 6:00 a.m. Eastern time) to liven up the channel offerings, Dr. Windecker observed, and to make them more immediate and potentially interactive.

Many of the parallel channels are devoted throughout the Congress to particular silos of cardiology; for example, arrhythmias and device therapy is on channel 3; CAD and acute care is on 5; HF is on 6; and preventive cardiology is on 9.

Other channels swing across different topics from day to day, such as channel 1, which covers COVID-19 topics on the first and third day of the meeting, “advances in science” on day 2, and “digital health, public health, health economics” on day 4.

The focus each day, starting at 2:00 p.m. CET (8:00 a.m. ET) and continuing into the evening in Europe, shifts over to the Prime Time live program, which features the Hot Line and guideline presentations and many of the live abstract presentations.

Dr. Kosiborod, not a researcher with the EMPEROR trials, is chair of the Dapagliflozin in Preserved Ejection Fraction Heart Failure ( PRESERVED-HF ) trial, which is scheduled for presentation at the September 2021 Heart Failure Society of American meeting.

A version of this article first appeared on Medscape.com.

Bimekizumab has been approved by the European Commission for the treatment of moderate to severe plaque psoriasis in adults, according to a statement from the manufacturer.

Bimekizumab (Bimzelx), a humanized IgG1 monoclonal antibody, is the first approved treatment for moderate to severe plaque psoriasis that selectively inhibits interleukin (IL)–17A and IL-17F, the statement from UCB said.

In the United States, the Food and Drug Administration is expected to make a decision on approval of bimekizumab for treating psoriasis on Oct. 15.

Approval in the EU was based on data from three phase 3 trials including a total of 1,480 adult patients with moderate to severe psoriasis, which found that those treated with bimekizumab experienced significantly greater skin clearance, compared with placebo, ustekinumab, and adalimumab, with a favorable safety profile, according to the company.

In all three studies (BE VIVID, BE READY, and BE SURE), more than 80% of patients treated with bimekizumab showed improved skin clearance after 16 weeks, significantly more than those treated with ustekinumab, placebo, or adalimumab, based on an improvement of at least 90% in the Psoriasis Area & Severity Index (PASI 90) and an Investigator’s Global Assessment (IGA) response of clear or almost clear skin (IGA 0/1). In all three studies, these clinical responses persisted after 1 year.

The recommended dose of bimekizumab is 320 mg, given in two subcutaneous injections every 4 weeks to week 16, then every 8 weeks. However, for “some patients” weighing 120 kg or more who have not achieved complete skin clearance at 16 weeks, 320 mg every 4 weeks after that time may improve response to treatment, according to the company statement.

The most common treatment-related adverse events in the studies were upper respiratory tract infections (a majority of which were nasopharyngitis), reported by 14.5% of patients, followed by oral candidiasis, reported by 7.3%.

Results of BE READY and BE VIVID were published in The Lancet. Results of the BE SURE study were published in The New England Journal of Medicine.

Bimekizumab is contraindicated for individuals with clinically important active infections such as tuberculosis, and for individuals with any hypersensitivity to the active substance. More details on bimekizumab are available on the website of the European Medicines Agency.

Bimekizumab has been approved by the European Commission for the treatment of moderate to severe plaque psoriasis in adults, according to a statement from the manufacturer.

Bimekizumab (Bimzelx), a humanized IgG1 monoclonal antibody, is the first approved treatment for moderate to severe plaque psoriasis that selectively inhibits interleukin (IL)–17A and IL-17F, the statement from UCB said.

In the United States, the Food and Drug Administration is expected to make a decision on approval of bimekizumab for treating psoriasis on Oct. 15.

Approval in the EU was based on data from three phase 3 trials including a total of 1,480 adult patients with moderate to severe psoriasis, which found that those treated with bimekizumab experienced significantly greater skin clearance, compared with placebo, ustekinumab, and adalimumab, with a favorable safety profile, according to the company.

In all three studies (BE VIVID, BE READY, and BE SURE), more than 80% of patients treated with bimekizumab showed improved skin clearance after 16 weeks, significantly more than those treated with ustekinumab, placebo, or adalimumab, based on an improvement of at least 90% in the Psoriasis Area & Severity Index (PASI 90) and an Investigator’s Global Assessment (IGA) response of clear or almost clear skin (IGA 0/1). In all three studies, these clinical responses persisted after 1 year.

The recommended dose of bimekizumab is 320 mg, given in two subcutaneous injections every 4 weeks to week 16, then every 8 weeks. However, for “some patients” weighing 120 kg or more who have not achieved complete skin clearance at 16 weeks, 320 mg every 4 weeks after that time may improve response to treatment, according to the company statement.

The most common treatment-related adverse events in the studies were upper respiratory tract infections (a majority of which were nasopharyngitis), reported by 14.5% of patients, followed by oral candidiasis, reported by 7.3%.

Results of BE READY and BE VIVID were published in The Lancet. Results of the BE SURE study were published in The New England Journal of Medicine.

Bimekizumab is contraindicated for individuals with clinically important active infections such as tuberculosis, and for individuals with any hypersensitivity to the active substance. More details on bimekizumab are available on the website of the European Medicines Agency.

Bimekizumab has been approved by the European Commission for the treatment of moderate to severe plaque psoriasis in adults, according to a statement from the manufacturer.

Bimekizumab (Bimzelx), a humanized IgG1 monoclonal antibody, is the first approved treatment for moderate to severe plaque psoriasis that selectively inhibits interleukin (IL)–17A and IL-17F, the statement from UCB said.

In the United States, the Food and Drug Administration is expected to make a decision on approval of bimekizumab for treating psoriasis on Oct. 15.

Approval in the EU was based on data from three phase 3 trials including a total of 1,480 adult patients with moderate to severe psoriasis, which found that those treated with bimekizumab experienced significantly greater skin clearance, compared with placebo, ustekinumab, and adalimumab, with a favorable safety profile, according to the company.

In all three studies (BE VIVID, BE READY, and BE SURE), more than 80% of patients treated with bimekizumab showed improved skin clearance after 16 weeks, significantly more than those treated with ustekinumab, placebo, or adalimumab, based on an improvement of at least 90% in the Psoriasis Area & Severity Index (PASI 90) and an Investigator’s Global Assessment (IGA) response of clear or almost clear skin (IGA 0/1). In all three studies, these clinical responses persisted after 1 year.

The recommended dose of bimekizumab is 320 mg, given in two subcutaneous injections every 4 weeks to week 16, then every 8 weeks. However, for “some patients” weighing 120 kg or more who have not achieved complete skin clearance at 16 weeks, 320 mg every 4 weeks after that time may improve response to treatment, according to the company statement.

The most common treatment-related adverse events in the studies were upper respiratory tract infections (a majority of which were nasopharyngitis), reported by 14.5% of patients, followed by oral candidiasis, reported by 7.3%.

Results of BE READY and BE VIVID were published in The Lancet. Results of the BE SURE study were published in The New England Journal of Medicine.

Bimekizumab is contraindicated for individuals with clinically important active infections such as tuberculosis, and for individuals with any hypersensitivity to the active substance. More details on bimekizumab are available on the website of the European Medicines Agency.

In this month’s column we continue to discuss recommendations from the gynecologic oncologist to the general gynecologist.

Don’t screen average-risk women for ovarian cancer.

Ovarian cancer is most often diagnosed at an advanced stage, which limits the curability of the disease. Consequently, there is a strong focus on attempting to diagnose the disease at earlier, more curable stages. This leads to the impulse by some well-intentioned providers to implement screening tests, such as ultrasounds and tumor markers, for all women. Unfortunately, the screening of “average risk” women for ovarian cancer is not recommended. Randomized controlled trials of tens of thousands of women have not observed a clinically significant decrease in ovarian cancer mortality with the addition of screening with tumor markers and ultrasound.¹ These studies did observe a false-positive rate of 5%. While that may seem like a low rate of false-positive testing, the definitive diagnostic test which follows is a major abdominal surgery (oophorectomy) and serious complications are encountered in 15% of patients undergoing surgery for false-positive ovarian cancer screening.¹ Therefore, quite simply, the harms are not balanced by benefits.

The key to offering patients appropriate and effective screening is case selection. It is important to identify which patients are at higher risk for ovarian cancer and offer those women testing for germline mutations and screening strategies. An important component of a well-woman visit is to take a thorough family history of cancer. Women are considered at high risk for having hereditary predisposition to ovarian cancer if they have a first- or second-degree relative with breast cancer younger than 45-50 years, or any age if Ashkenazi Jewish, triple-negative breast cancer younger than 60 years of age, two or more primary breast cancers with the first diagnosed at less than 50 years of age, male breast cancer, ovarian cancer, pancreatic cancer, a known BRCA 1/2 mutation, or a personal history of those same conditions. These women should be recommended to undergo genetic testing for BRCA 1, 2, and Lynch syndrome. They should not automatically be offered ovarian cancer screening. If a patient has a more remote family history for ovarian cancer, their personal risk may be somewhat elevated above the baseline population risk, however, not substantially enough to justify implementing screening in the absence of a confirmed genetic mutation.

While screening tests may not be appropriate for all patients, all patients should be asked about the early symptoms of ovarian cancer because these are consistently present, and frequently overlooked, prior to the eventual diagnosis of advanced disease. Those symptoms include abdominal discomfort, abdominal swelling and bloating, and urinary urgency.² Consider offering all patients a dedicated ovarian cancer specific review of systems that includes inquiries about these symptoms at their annual wellness visits.
 

Opt for vertical midline incisions when surgery is anticipated to be complex

What is the first thing gynecologic oncologists do when called in to assist in a difficult gynecologic procedure? Get better exposure. Exposure is the cornerstone of safe, effective surgery. Sometimes this simply means placing a more effective retractor. In other cases, it might mean extending the incision. However, if the incision is a low transverse incision (the go-to for many gynecologists because of its favorable cosmetic and pain-producing profile) this proves to be difficult. Attempting to assist in a complicated case, such as a frozen pelvis, severed ureter or rectal injury, through a pfannensteil incision can be extraordinarily difficult, and while these incisions can be extended by incising the rectus muscle bellies, upper abdominal visualization remains elusive in most patients. This is particularly problematic if the ureter or splenic flexure need to be mobilized, or if extensive lysis of adhesions is necessary to ensure there is no occult enterotomy. As my mentor Dr. John Soper once described to me: “It’s like trying to scratch your armpit by reaching through your fly.”

While pfannensteil incisions come naturally, and comfortably, to most gynecologists, likely because of their frequent application during cesarean section, all gynecologists should be confident in the steps and anatomy for vertical midline, or paramedian incisions. This is not only beneficial for complex gynecologic cases, but also in the event of vascular emergency. In the hands of an experienced abdominal/pelvic surgeon, the vertical midline incision is the quickest way to safely enter the abdomen, and provides the kind of exposure that may be critical in safely repairing or controlling hemorrhage from a major vessel.

While low transverse incisions may be more cosmetic, less painful, and associated with fewer wound complications, our first concern as surgeons should be mitigating complications. In situations where risks of complications are high, it is best to not handicap ourselves with the incision location. And always remember, wound complications are highest when a transverse incision needs to be converted to a vertical one with a “T.”
 

It’s not just about diagnosis of cancer, it’s also prevention

Detection of cancer is an important role of the obstetrician gynecologist. However, equally important is being able to seize opportunities for cancer prevention. Cervical, vulvar, endometrial and ovarian cancer are all known to have preventative strategies.

All patients up to the age of 45 should be offered vaccination against HPV. Initial indications for HPV vaccination were for women up to age 26; however, recent data support the safety and efficacy of the vaccine in older women.³ HPV vaccination is most effective at preventing cancer when administered prior to exposure (ideally age 9-11), leaving this in the hands of our pediatrician colleagues. However, we must be vigilant to inquire about vaccination status for all our patients and encourage vaccines for those who were missed earlier in their life.

Patients should be counseled regarding the significant risk reduction for cancer that is gained from use of oral hormonal contraceptives and progestin-releasing IUDs (especially for endometrial and ovarian cancers). Providing them with knowledge of this information when considering options for contraception or menstrual cycle management is important in their decision-making process.

Endometrial cancer incidence is sadly on the rise in the United States, likely secondary to increasing rates of obesity. Pregnancy is a time when many women begin to gain, and accumulate, weight and therefore obstetric providers have a unique opportunity to assist patients in strategies to normalize their weight after pregnancy. Many of my patients with endometrial cancer state that they have never heard that it is associated with obesity. This suggests that more can be done to educate patients on the carcinogenic effect of obesity (for both endometrial and breast cancer), which may aid in motivating change of modifiable behaviors.

The fallopian tubes are the source of many ovarian cancers and knowledge of this has led to the recommendation to perform opportunistic salpingectomy as a cancer risk-reducing strategy. Hysterectomy and sterilization procedures are most apropos for this modification. While prospective data to confirm a reduced risk of ovarian cancer with opportunistic salpingectomy are lacking, a reduced incidence of cancer has been observed when the tubes have been removed for indicated surgeries; there appear to be no significant deleterious sequelae.^4,5 A focus should be made on removal of the entire distal third of the tube, particularly the fimbriated ends, as this is the portion most implicated in malignancy.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no relevant disclosures. Contact her at [email protected].
 

References

1. Buys SS et al. JAMA. 2011;305(22):2295.

2. Goff BA et al. JAMA. 2004;291(22):2705.

3. Castellsagué X et al. Br J Cancer. 2011;105(1):28.

4. Yoon SH et al. Eur J Cancer. 2016 Mar;55:38-46.

5. Hanley GE et al. Am J Obstet Gynecol. 2018;219(2):172.

In this month’s column we continue to discuss recommendations from the gynecologic oncologist to the general gynecologist.

Don’t screen average-risk women for ovarian cancer.

Ovarian cancer is most often diagnosed at an advanced stage, which limits the curability of the disease. Consequently, there is a strong focus on attempting to diagnose the disease at earlier, more curable stages. This leads to the impulse by some well-intentioned providers to implement screening tests, such as ultrasounds and tumor markers, for all women. Unfortunately, the screening of “average risk” women for ovarian cancer is not recommended. Randomized controlled trials of tens of thousands of women have not observed a clinically significant decrease in ovarian cancer mortality with the addition of screening with tumor markers and ultrasound.¹ These studies did observe a false-positive rate of 5%. While that may seem like a low rate of false-positive testing, the definitive diagnostic test which follows is a major abdominal surgery (oophorectomy) and serious complications are encountered in 15% of patients undergoing surgery for false-positive ovarian cancer screening.¹ Therefore, quite simply, the harms are not balanced by benefits.

The key to offering patients appropriate and effective screening is case selection. It is important to identify which patients are at higher risk for ovarian cancer and offer those women testing for germline mutations and screening strategies. An important component of a well-woman visit is to take a thorough family history of cancer. Women are considered at high risk for having hereditary predisposition to ovarian cancer if they have a first- or second-degree relative with breast cancer younger than 45-50 years, or any age if Ashkenazi Jewish, triple-negative breast cancer younger than 60 years of age, two or more primary breast cancers with the first diagnosed at less than 50 years of age, male breast cancer, ovarian cancer, pancreatic cancer, a known BRCA 1/2 mutation, or a personal history of those same conditions. These women should be recommended to undergo genetic testing for BRCA 1, 2, and Lynch syndrome. They should not automatically be offered ovarian cancer screening. If a patient has a more remote family history for ovarian cancer, their personal risk may be somewhat elevated above the baseline population risk, however, not substantially enough to justify implementing screening in the absence of a confirmed genetic mutation.

While screening tests may not be appropriate for all patients, all patients should be asked about the early symptoms of ovarian cancer because these are consistently present, and frequently overlooked, prior to the eventual diagnosis of advanced disease. Those symptoms include abdominal discomfort, abdominal swelling and bloating, and urinary urgency.² Consider offering all patients a dedicated ovarian cancer specific review of systems that includes inquiries about these symptoms at their annual wellness visits.
 

Opt for vertical midline incisions when surgery is anticipated to be complex

What is the first thing gynecologic oncologists do when called in to assist in a difficult gynecologic procedure? Get better exposure. Exposure is the cornerstone of safe, effective surgery. Sometimes this simply means placing a more effective retractor. In other cases, it might mean extending the incision. However, if the incision is a low transverse incision (the go-to for many gynecologists because of its favorable cosmetic and pain-producing profile) this proves to be difficult. Attempting to assist in a complicated case, such as a frozen pelvis, severed ureter or rectal injury, through a pfannensteil incision can be extraordinarily difficult, and while these incisions can be extended by incising the rectus muscle bellies, upper abdominal visualization remains elusive in most patients. This is particularly problematic if the ureter or splenic flexure need to be mobilized, or if extensive lysis of adhesions is necessary to ensure there is no occult enterotomy. As my mentor Dr. John Soper once described to me: “It’s like trying to scratch your armpit by reaching through your fly.”

While pfannensteil incisions come naturally, and comfortably, to most gynecologists, likely because of their frequent application during cesarean section, all gynecologists should be confident in the steps and anatomy for vertical midline, or paramedian incisions. This is not only beneficial for complex gynecologic cases, but also in the event of vascular emergency. In the hands of an experienced abdominal/pelvic surgeon, the vertical midline incision is the quickest way to safely enter the abdomen, and provides the kind of exposure that may be critical in safely repairing or controlling hemorrhage from a major vessel.

While low transverse incisions may be more cosmetic, less painful, and associated with fewer wound complications, our first concern as surgeons should be mitigating complications. In situations where risks of complications are high, it is best to not handicap ourselves with the incision location. And always remember, wound complications are highest when a transverse incision needs to be converted to a vertical one with a “T.”
 

It’s not just about diagnosis of cancer, it’s also prevention

Detection of cancer is an important role of the obstetrician gynecologist. However, equally important is being able to seize opportunities for cancer prevention. Cervical, vulvar, endometrial and ovarian cancer are all known to have preventative strategies.

All patients up to the age of 45 should be offered vaccination against HPV. Initial indications for HPV vaccination were for women up to age 26; however, recent data support the safety and efficacy of the vaccine in older women.³ HPV vaccination is most effective at preventing cancer when administered prior to exposure (ideally age 9-11), leaving this in the hands of our pediatrician colleagues. However, we must be vigilant to inquire about vaccination status for all our patients and encourage vaccines for those who were missed earlier in their life.

Patients should be counseled regarding the significant risk reduction for cancer that is gained from use of oral hormonal contraceptives and progestin-releasing IUDs (especially for endometrial and ovarian cancers). Providing them with knowledge of this information when considering options for contraception or menstrual cycle management is important in their decision-making process.

Endometrial cancer incidence is sadly on the rise in the United States, likely secondary to increasing rates of obesity. Pregnancy is a time when many women begin to gain, and accumulate, weight and therefore obstetric providers have a unique opportunity to assist patients in strategies to normalize their weight after pregnancy. Many of my patients with endometrial cancer state that they have never heard that it is associated with obesity. This suggests that more can be done to educate patients on the carcinogenic effect of obesity (for both endometrial and breast cancer), which may aid in motivating change of modifiable behaviors.

The fallopian tubes are the source of many ovarian cancers and knowledge of this has led to the recommendation to perform opportunistic salpingectomy as a cancer risk-reducing strategy. Hysterectomy and sterilization procedures are most apropos for this modification. While prospective data to confirm a reduced risk of ovarian cancer with opportunistic salpingectomy are lacking, a reduced incidence of cancer has been observed when the tubes have been removed for indicated surgeries; there appear to be no significant deleterious sequelae.^4,5 A focus should be made on removal of the entire distal third of the tube, particularly the fimbriated ends, as this is the portion most implicated in malignancy.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no relevant disclosures. Contact her at [email protected].
 

References

1. Buys SS et al. JAMA. 2011;305(22):2295.

2. Goff BA et al. JAMA. 2004;291(22):2705.

3. Castellsagué X et al. Br J Cancer. 2011;105(1):28.

4. Yoon SH et al. Eur J Cancer. 2016 Mar;55:38-46.

5. Hanley GE et al. Am J Obstet Gynecol. 2018;219(2):172.

In this month’s column we continue to discuss recommendations from the gynecologic oncologist to the general gynecologist.

Don’t screen average-risk women for ovarian cancer.

Ovarian cancer is most often diagnosed at an advanced stage, which limits the curability of the disease. Consequently, there is a strong focus on attempting to diagnose the disease at earlier, more curable stages. This leads to the impulse by some well-intentioned providers to implement screening tests, such as ultrasounds and tumor markers, for all women. Unfortunately, the screening of “average risk” women for ovarian cancer is not recommended. Randomized controlled trials of tens of thousands of women have not observed a clinically significant decrease in ovarian cancer mortality with the addition of screening with tumor markers and ultrasound.¹ These studies did observe a false-positive rate of 5%. While that may seem like a low rate of false-positive testing, the definitive diagnostic test which follows is a major abdominal surgery (oophorectomy) and serious complications are encountered in 15% of patients undergoing surgery for false-positive ovarian cancer screening.¹ Therefore, quite simply, the harms are not balanced by benefits.

The key to offering patients appropriate and effective screening is case selection. It is important to identify which patients are at higher risk for ovarian cancer and offer those women testing for germline mutations and screening strategies. An important component of a well-woman visit is to take a thorough family history of cancer. Women are considered at high risk for having hereditary predisposition to ovarian cancer if they have a first- or second-degree relative with breast cancer younger than 45-50 years, or any age if Ashkenazi Jewish, triple-negative breast cancer younger than 60 years of age, two or more primary breast cancers with the first diagnosed at less than 50 years of age, male breast cancer, ovarian cancer, pancreatic cancer, a known BRCA 1/2 mutation, or a personal history of those same conditions. These women should be recommended to undergo genetic testing for BRCA 1, 2, and Lynch syndrome. They should not automatically be offered ovarian cancer screening. If a patient has a more remote family history for ovarian cancer, their personal risk may be somewhat elevated above the baseline population risk, however, not substantially enough to justify implementing screening in the absence of a confirmed genetic mutation.

While screening tests may not be appropriate for all patients, all patients should be asked about the early symptoms of ovarian cancer because these are consistently present, and frequently overlooked, prior to the eventual diagnosis of advanced disease. Those symptoms include abdominal discomfort, abdominal swelling and bloating, and urinary urgency.² Consider offering all patients a dedicated ovarian cancer specific review of systems that includes inquiries about these symptoms at their annual wellness visits.
 

Opt for vertical midline incisions when surgery is anticipated to be complex

What is the first thing gynecologic oncologists do when called in to assist in a difficult gynecologic procedure? Get better exposure. Exposure is the cornerstone of safe, effective surgery. Sometimes this simply means placing a more effective retractor. In other cases, it might mean extending the incision. However, if the incision is a low transverse incision (the go-to for many gynecologists because of its favorable cosmetic and pain-producing profile) this proves to be difficult. Attempting to assist in a complicated case, such as a frozen pelvis, severed ureter or rectal injury, through a pfannensteil incision can be extraordinarily difficult, and while these incisions can be extended by incising the rectus muscle bellies, upper abdominal visualization remains elusive in most patients. This is particularly problematic if the ureter or splenic flexure need to be mobilized, or if extensive lysis of adhesions is necessary to ensure there is no occult enterotomy. As my mentor Dr. John Soper once described to me: “It’s like trying to scratch your armpit by reaching through your fly.”

While pfannensteil incisions come naturally, and comfortably, to most gynecologists, likely because of their frequent application during cesarean section, all gynecologists should be confident in the steps and anatomy for vertical midline, or paramedian incisions. This is not only beneficial for complex gynecologic cases, but also in the event of vascular emergency. In the hands of an experienced abdominal/pelvic surgeon, the vertical midline incision is the quickest way to safely enter the abdomen, and provides the kind of exposure that may be critical in safely repairing or controlling hemorrhage from a major vessel.

While low transverse incisions may be more cosmetic, less painful, and associated with fewer wound complications, our first concern as surgeons should be mitigating complications. In situations where risks of complications are high, it is best to not handicap ourselves with the incision location. And always remember, wound complications are highest when a transverse incision needs to be converted to a vertical one with a “T.”
 

It’s not just about diagnosis of cancer, it’s also prevention

Detection of cancer is an important role of the obstetrician gynecologist. However, equally important is being able to seize opportunities for cancer prevention. Cervical, vulvar, endometrial and ovarian cancer are all known to have preventative strategies.

All patients up to the age of 45 should be offered vaccination against HPV. Initial indications for HPV vaccination were for women up to age 26; however, recent data support the safety and efficacy of the vaccine in older women.³ HPV vaccination is most effective at preventing cancer when administered prior to exposure (ideally age 9-11), leaving this in the hands of our pediatrician colleagues. However, we must be vigilant to inquire about vaccination status for all our patients and encourage vaccines for those who were missed earlier in their life.

Patients should be counseled regarding the significant risk reduction for cancer that is gained from use of oral hormonal contraceptives and progestin-releasing IUDs (especially for endometrial and ovarian cancers). Providing them with knowledge of this information when considering options for contraception or menstrual cycle management is important in their decision-making process.

Endometrial cancer incidence is sadly on the rise in the United States, likely secondary to increasing rates of obesity. Pregnancy is a time when many women begin to gain, and accumulate, weight and therefore obstetric providers have a unique opportunity to assist patients in strategies to normalize their weight after pregnancy. Many of my patients with endometrial cancer state that they have never heard that it is associated with obesity. This suggests that more can be done to educate patients on the carcinogenic effect of obesity (for both endometrial and breast cancer), which may aid in motivating change of modifiable behaviors.

The fallopian tubes are the source of many ovarian cancers and knowledge of this has led to the recommendation to perform opportunistic salpingectomy as a cancer risk-reducing strategy. Hysterectomy and sterilization procedures are most apropos for this modification. While prospective data to confirm a reduced risk of ovarian cancer with opportunistic salpingectomy are lacking, a reduced incidence of cancer has been observed when the tubes have been removed for indicated surgeries; there appear to be no significant deleterious sequelae.^4,5 A focus should be made on removal of the entire distal third of the tube, particularly the fimbriated ends, as this is the portion most implicated in malignancy.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no relevant disclosures. Contact her at [email protected].
 

References

1. Buys SS et al. JAMA. 2011;305(22):2295.

2. Goff BA et al. JAMA. 2004;291(22):2705.

3. Castellsagué X et al. Br J Cancer. 2011;105(1):28.

4. Yoon SH et al. Eur J Cancer. 2016 Mar;55:38-46.

5. Hanley GE et al. Am J Obstet Gynecol. 2018;219(2):172.