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FDA okays difelikefalin for dialysis-associated pruritus in patients with CKD
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.
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.
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.
Eyes on ESC ‘21: Hope for EMPEROR-Preserved, guidelines remade
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.
U.S. kidney transplants grow in number and success
During 2016-2019, U.S. centers performed kidney transplants in nearly 77,000 patients, a jump of almost 25% compared with 4-year averages of about 62,000 patients throughout 2004-2015. That works out to about 15,000 more patients receiving donor kidneys, Sundaram Hariharan, MD, and associates reported in the New England Journal of Medicine in a review of all U.S. renal transplantations performed during 1996-2019.
Coupled with the volume uptick during this 24-year period were new lows in graft losses and patient deaths. By 2018, mortality during the first year following transplantation occurred at about a 1% rate among patients who had received a kidney from a living donor, and at about a 3% rate when the organ came from a deceased donor, nearly half the rate of 2 decades earlier, in 1996. Rates of first-year graft loss during 2017 were also about half of what they had been in 1996, occurring in about 2% of patients who received a living donor organ and in about 6% of those who got a kidney from a deceased donor during 2017.
“Twenty years ago, kidney transplantation was the preferred option compared with dialysis, and even more so now,” summed up Dr. Hariharan, a senior transplant nephrologist and professor of medicine and surgery at the University of Pittsburgh Medical Center and first author of the report. Kidney transplantation survival at U.S. centers “improved steadily over the past 24 years, despite patient variables becoming worse,” he said in an interview.
Kidney recipients are older, more obese, and have more prevalent diabetes
During the period studied, kidney transplant recipients became on average older and more obese, and had a higher prevalence of diabetes; the age of organ donors grew as well. The prevalence of diabetes among patients who received a kidney from a deceased donor increased from 24% during 1996-1999 to 36% during 2016-2019, while diabetes prevalence among recipients of an organ from a living donor rose from 25% in 1996-1999 to 29% during 2016-2019.
The improved graft and patient survival numbers “are very encouraging trends,” said Michelle A. Josephson, MD, professor and medical director of kidney transplantation at the University of Chicago, who was not involved with the report. “We have been hearing for a number of years that short-term graft survival had improved, but I’m thrilled to learn that long-term survival has also improved.”
The report documented 10-year survival of graft recipients during 2008-2011 of 67%, up from 61% during 1996-1999, and a 10-year overall graft survival rate of 54% in the 2008-2011 cohort, an improvement from the 42% rate in patients who received their organs in 1996-1999, changes Dr. Hariharan characterized as “modest.”
These improvements in long-term graft and patient survival are “meaningful, and particularly notable that outcomes improved despite increased complexity of the transplant population,” said Krista L. Lentine, MD, PhD, professor and medical director of living donation at Saint Louis University. But “despite these improvements, long-term graft survival remains limited,” she cautioned, especially because of risks for substantial complications from chronic immunosuppressive treatment including infection, cancer, glucose intolerance, and dyslipidemia.
The analysis reported by Dr. Hariharan and his associates used data collected by the Scientific Registry of Transplant Patients, run under contract with the U.S. Department of Health and Human Services, which has tracked all patients who have had kidney transplants at U.S. centers since the late 1980s, said Dr. Hariharan. The database included just over 362,000 total transplants during the 24-year period studied, with 36% of all transplants involving organs from living donors with the remaining patients receiving kidneys from deceased donors.
Living donations still stagnant; deceased-donor kidneys rise
The data showed that the rate of transplants from living donors was stagnant for 2 decades, with 22,525 patients transplanted during 2000-2003, and 23,746 transplanted during 2016-2019, with very similar rates during the intervening years. The recent spurt in transplants during 2016-2019 compared with the preceding decade depended almost entirely on kidneys from deceased donors. This rate jumped from the steady, slow rise it showed during 1996-2015, when deceased-donor transplants rose from about 30,000 during 1996-1999 to about 41,000 during 2012-2015, to a more dramatic increase of about 12,000 additional transplants during the most recent period, adding up to a total of more than 53,000 transplants from deceased donors during 2016-2019.
“I strongly recommend organs from living donors” when feasible, said Dr. Hariharan. “At some centers, a high proportion of transplants use living donors, but not at other centers,” he said.
It’s unknown why transplants using organs from deceased donors has shown this growth, but Dr. Hariharan suggested a multifactorial explanation. Those factors include growth in the number of patients with end-stage renal disease who require dialysis, increased numbers of patients listed for kidney transplant, new approaches that allow organs from older donors and those infected with pathogens such as hepatitis C virus or HIV, greater numbers of people and families agreeing to donate organs, and possibly the opioid crisis that may have led to increased organ donation. The number of U.S. centers performing kidney transplants rose from fewer than 200 about a quarter of a century ago to about 250 today, he added.
‘Immuno Bill’ guarantees Medicare coverage for immunosuppression
Dr. Hariharan voiced optimism that graft and patient survival rates will continue to improve going forward. One factor will likely be the passage in late 2020 of the “Immuno Bill” by the U.S. Congress, which among other things mandated ongoing coverage starting in 2023 for immunosuppressive drugs for all Medicare beneficiaries with a kidney transplant. Until then, Medicare provides coverage for only 36 months, a time limit that has resulted in nearly 400 kidney recipients annually losing coverage of their immunosuppression medications.
Dr. Hariharan and coauthors called the existing potential for discontinuation of immunosuppressive drug an “unnecessary impediment to long-term survival for which patients and society paid a heavy price.”
“Kidney transplantation, especially from living donors, offers patients with kidney failure the best chance for long-term survival and improved quality of life, with lower cost to the health care system,” Dr. Lentine said in an interview. Despite the many positive trends detailed in the report from Dr. Hariharan and coauthors, “the vast majority of the more than 700,000 people in the United States with kidney failure will not have an opportunity to receive a transplant due to limitations in organ supply.” And many patients who receive a kidney transplant eventually must resume dialysis because of “limited long-term graft survival resulting from allograft nephropathy, recurrent native disease, medication nonadherence, or other causes.” Plus many potentially transplantable organs go unused.
Dr. Lentine cited a position statement issued in July 2021 by the National Kidney Foundation that made several recommendations on how to improve access to kidney transplants and improve outcomes. “Expanding opportunities for safe living donation, eliminating racial disparities in living-donor access, improving wait-list access and transport readiness, maximizing use of deceased-donor organs, and extending graft longevity are critical priorities,” said Dr. Lentine, lead author on the statement.
“For many or even most patients with kidney failure transplantation is the optimal form of renal replacement. The better recent outcomes and evolving management strategies make transplantation an even more attractive option,” said Dr. Josephson. Improved outcomes among U.S. transplant patients also highlights the “importance of increasing access to kidney transplantation” for all people with kidney failure who could benefit from this treatment, she added.
Dr. Hariharan and Dr. Lentine had no relevant disclosures. Dr. Josephson has been a consultant to UCB and has an ownership interest in Seagen.
During 2016-2019, U.S. centers performed kidney transplants in nearly 77,000 patients, a jump of almost 25% compared with 4-year averages of about 62,000 patients throughout 2004-2015. That works out to about 15,000 more patients receiving donor kidneys, Sundaram Hariharan, MD, and associates reported in the New England Journal of Medicine in a review of all U.S. renal transplantations performed during 1996-2019.
Coupled with the volume uptick during this 24-year period were new lows in graft losses and patient deaths. By 2018, mortality during the first year following transplantation occurred at about a 1% rate among patients who had received a kidney from a living donor, and at about a 3% rate when the organ came from a deceased donor, nearly half the rate of 2 decades earlier, in 1996. Rates of first-year graft loss during 2017 were also about half of what they had been in 1996, occurring in about 2% of patients who received a living donor organ and in about 6% of those who got a kidney from a deceased donor during 2017.
“Twenty years ago, kidney transplantation was the preferred option compared with dialysis, and even more so now,” summed up Dr. Hariharan, a senior transplant nephrologist and professor of medicine and surgery at the University of Pittsburgh Medical Center and first author of the report. Kidney transplantation survival at U.S. centers “improved steadily over the past 24 years, despite patient variables becoming worse,” he said in an interview.
Kidney recipients are older, more obese, and have more prevalent diabetes
During the period studied, kidney transplant recipients became on average older and more obese, and had a higher prevalence of diabetes; the age of organ donors grew as well. The prevalence of diabetes among patients who received a kidney from a deceased donor increased from 24% during 1996-1999 to 36% during 2016-2019, while diabetes prevalence among recipients of an organ from a living donor rose from 25% in 1996-1999 to 29% during 2016-2019.
The improved graft and patient survival numbers “are very encouraging trends,” said Michelle A. Josephson, MD, professor and medical director of kidney transplantation at the University of Chicago, who was not involved with the report. “We have been hearing for a number of years that short-term graft survival had improved, but I’m thrilled to learn that long-term survival has also improved.”
The report documented 10-year survival of graft recipients during 2008-2011 of 67%, up from 61% during 1996-1999, and a 10-year overall graft survival rate of 54% in the 2008-2011 cohort, an improvement from the 42% rate in patients who received their organs in 1996-1999, changes Dr. Hariharan characterized as “modest.”
These improvements in long-term graft and patient survival are “meaningful, and particularly notable that outcomes improved despite increased complexity of the transplant population,” said Krista L. Lentine, MD, PhD, professor and medical director of living donation at Saint Louis University. But “despite these improvements, long-term graft survival remains limited,” she cautioned, especially because of risks for substantial complications from chronic immunosuppressive treatment including infection, cancer, glucose intolerance, and dyslipidemia.
The analysis reported by Dr. Hariharan and his associates used data collected by the Scientific Registry of Transplant Patients, run under contract with the U.S. Department of Health and Human Services, which has tracked all patients who have had kidney transplants at U.S. centers since the late 1980s, said Dr. Hariharan. The database included just over 362,000 total transplants during the 24-year period studied, with 36% of all transplants involving organs from living donors with the remaining patients receiving kidneys from deceased donors.
Living donations still stagnant; deceased-donor kidneys rise
The data showed that the rate of transplants from living donors was stagnant for 2 decades, with 22,525 patients transplanted during 2000-2003, and 23,746 transplanted during 2016-2019, with very similar rates during the intervening years. The recent spurt in transplants during 2016-2019 compared with the preceding decade depended almost entirely on kidneys from deceased donors. This rate jumped from the steady, slow rise it showed during 1996-2015, when deceased-donor transplants rose from about 30,000 during 1996-1999 to about 41,000 during 2012-2015, to a more dramatic increase of about 12,000 additional transplants during the most recent period, adding up to a total of more than 53,000 transplants from deceased donors during 2016-2019.
“I strongly recommend organs from living donors” when feasible, said Dr. Hariharan. “At some centers, a high proportion of transplants use living donors, but not at other centers,” he said.
It’s unknown why transplants using organs from deceased donors has shown this growth, but Dr. Hariharan suggested a multifactorial explanation. Those factors include growth in the number of patients with end-stage renal disease who require dialysis, increased numbers of patients listed for kidney transplant, new approaches that allow organs from older donors and those infected with pathogens such as hepatitis C virus or HIV, greater numbers of people and families agreeing to donate organs, and possibly the opioid crisis that may have led to increased organ donation. The number of U.S. centers performing kidney transplants rose from fewer than 200 about a quarter of a century ago to about 250 today, he added.
‘Immuno Bill’ guarantees Medicare coverage for immunosuppression
Dr. Hariharan voiced optimism that graft and patient survival rates will continue to improve going forward. One factor will likely be the passage in late 2020 of the “Immuno Bill” by the U.S. Congress, which among other things mandated ongoing coverage starting in 2023 for immunosuppressive drugs for all Medicare beneficiaries with a kidney transplant. Until then, Medicare provides coverage for only 36 months, a time limit that has resulted in nearly 400 kidney recipients annually losing coverage of their immunosuppression medications.
Dr. Hariharan and coauthors called the existing potential for discontinuation of immunosuppressive drug an “unnecessary impediment to long-term survival for which patients and society paid a heavy price.”
“Kidney transplantation, especially from living donors, offers patients with kidney failure the best chance for long-term survival and improved quality of life, with lower cost to the health care system,” Dr. Lentine said in an interview. Despite the many positive trends detailed in the report from Dr. Hariharan and coauthors, “the vast majority of the more than 700,000 people in the United States with kidney failure will not have an opportunity to receive a transplant due to limitations in organ supply.” And many patients who receive a kidney transplant eventually must resume dialysis because of “limited long-term graft survival resulting from allograft nephropathy, recurrent native disease, medication nonadherence, or other causes.” Plus many potentially transplantable organs go unused.
Dr. Lentine cited a position statement issued in July 2021 by the National Kidney Foundation that made several recommendations on how to improve access to kidney transplants and improve outcomes. “Expanding opportunities for safe living donation, eliminating racial disparities in living-donor access, improving wait-list access and transport readiness, maximizing use of deceased-donor organs, and extending graft longevity are critical priorities,” said Dr. Lentine, lead author on the statement.
“For many or even most patients with kidney failure transplantation is the optimal form of renal replacement. The better recent outcomes and evolving management strategies make transplantation an even more attractive option,” said Dr. Josephson. Improved outcomes among U.S. transplant patients also highlights the “importance of increasing access to kidney transplantation” for all people with kidney failure who could benefit from this treatment, she added.
Dr. Hariharan and Dr. Lentine had no relevant disclosures. Dr. Josephson has been a consultant to UCB and has an ownership interest in Seagen.
During 2016-2019, U.S. centers performed kidney transplants in nearly 77,000 patients, a jump of almost 25% compared with 4-year averages of about 62,000 patients throughout 2004-2015. That works out to about 15,000 more patients receiving donor kidneys, Sundaram Hariharan, MD, and associates reported in the New England Journal of Medicine in a review of all U.S. renal transplantations performed during 1996-2019.
Coupled with the volume uptick during this 24-year period were new lows in graft losses and patient deaths. By 2018, mortality during the first year following transplantation occurred at about a 1% rate among patients who had received a kidney from a living donor, and at about a 3% rate when the organ came from a deceased donor, nearly half the rate of 2 decades earlier, in 1996. Rates of first-year graft loss during 2017 were also about half of what they had been in 1996, occurring in about 2% of patients who received a living donor organ and in about 6% of those who got a kidney from a deceased donor during 2017.
“Twenty years ago, kidney transplantation was the preferred option compared with dialysis, and even more so now,” summed up Dr. Hariharan, a senior transplant nephrologist and professor of medicine and surgery at the University of Pittsburgh Medical Center and first author of the report. Kidney transplantation survival at U.S. centers “improved steadily over the past 24 years, despite patient variables becoming worse,” he said in an interview.
Kidney recipients are older, more obese, and have more prevalent diabetes
During the period studied, kidney transplant recipients became on average older and more obese, and had a higher prevalence of diabetes; the age of organ donors grew as well. The prevalence of diabetes among patients who received a kidney from a deceased donor increased from 24% during 1996-1999 to 36% during 2016-2019, while diabetes prevalence among recipients of an organ from a living donor rose from 25% in 1996-1999 to 29% during 2016-2019.
The improved graft and patient survival numbers “are very encouraging trends,” said Michelle A. Josephson, MD, professor and medical director of kidney transplantation at the University of Chicago, who was not involved with the report. “We have been hearing for a number of years that short-term graft survival had improved, but I’m thrilled to learn that long-term survival has also improved.”
The report documented 10-year survival of graft recipients during 2008-2011 of 67%, up from 61% during 1996-1999, and a 10-year overall graft survival rate of 54% in the 2008-2011 cohort, an improvement from the 42% rate in patients who received their organs in 1996-1999, changes Dr. Hariharan characterized as “modest.”
These improvements in long-term graft and patient survival are “meaningful, and particularly notable that outcomes improved despite increased complexity of the transplant population,” said Krista L. Lentine, MD, PhD, professor and medical director of living donation at Saint Louis University. But “despite these improvements, long-term graft survival remains limited,” she cautioned, especially because of risks for substantial complications from chronic immunosuppressive treatment including infection, cancer, glucose intolerance, and dyslipidemia.
The analysis reported by Dr. Hariharan and his associates used data collected by the Scientific Registry of Transplant Patients, run under contract with the U.S. Department of Health and Human Services, which has tracked all patients who have had kidney transplants at U.S. centers since the late 1980s, said Dr. Hariharan. The database included just over 362,000 total transplants during the 24-year period studied, with 36% of all transplants involving organs from living donors with the remaining patients receiving kidneys from deceased donors.
Living donations still stagnant; deceased-donor kidneys rise
The data showed that the rate of transplants from living donors was stagnant for 2 decades, with 22,525 patients transplanted during 2000-2003, and 23,746 transplanted during 2016-2019, with very similar rates during the intervening years. The recent spurt in transplants during 2016-2019 compared with the preceding decade depended almost entirely on kidneys from deceased donors. This rate jumped from the steady, slow rise it showed during 1996-2015, when deceased-donor transplants rose from about 30,000 during 1996-1999 to about 41,000 during 2012-2015, to a more dramatic increase of about 12,000 additional transplants during the most recent period, adding up to a total of more than 53,000 transplants from deceased donors during 2016-2019.
“I strongly recommend organs from living donors” when feasible, said Dr. Hariharan. “At some centers, a high proportion of transplants use living donors, but not at other centers,” he said.
It’s unknown why transplants using organs from deceased donors has shown this growth, but Dr. Hariharan suggested a multifactorial explanation. Those factors include growth in the number of patients with end-stage renal disease who require dialysis, increased numbers of patients listed for kidney transplant, new approaches that allow organs from older donors and those infected with pathogens such as hepatitis C virus or HIV, greater numbers of people and families agreeing to donate organs, and possibly the opioid crisis that may have led to increased organ donation. The number of U.S. centers performing kidney transplants rose from fewer than 200 about a quarter of a century ago to about 250 today, he added.
‘Immuno Bill’ guarantees Medicare coverage for immunosuppression
Dr. Hariharan voiced optimism that graft and patient survival rates will continue to improve going forward. One factor will likely be the passage in late 2020 of the “Immuno Bill” by the U.S. Congress, which among other things mandated ongoing coverage starting in 2023 for immunosuppressive drugs for all Medicare beneficiaries with a kidney transplant. Until then, Medicare provides coverage for only 36 months, a time limit that has resulted in nearly 400 kidney recipients annually losing coverage of their immunosuppression medications.
Dr. Hariharan and coauthors called the existing potential for discontinuation of immunosuppressive drug an “unnecessary impediment to long-term survival for which patients and society paid a heavy price.”
“Kidney transplantation, especially from living donors, offers patients with kidney failure the best chance for long-term survival and improved quality of life, with lower cost to the health care system,” Dr. Lentine said in an interview. Despite the many positive trends detailed in the report from Dr. Hariharan and coauthors, “the vast majority of the more than 700,000 people in the United States with kidney failure will not have an opportunity to receive a transplant due to limitations in organ supply.” And many patients who receive a kidney transplant eventually must resume dialysis because of “limited long-term graft survival resulting from allograft nephropathy, recurrent native disease, medication nonadherence, or other causes.” Plus many potentially transplantable organs go unused.
Dr. Lentine cited a position statement issued in July 2021 by the National Kidney Foundation that made several recommendations on how to improve access to kidney transplants and improve outcomes. “Expanding opportunities for safe living donation, eliminating racial disparities in living-donor access, improving wait-list access and transport readiness, maximizing use of deceased-donor organs, and extending graft longevity are critical priorities,” said Dr. Lentine, lead author on the statement.
“For many or even most patients with kidney failure transplantation is the optimal form of renal replacement. The better recent outcomes and evolving management strategies make transplantation an even more attractive option,” said Dr. Josephson. Improved outcomes among U.S. transplant patients also highlights the “importance of increasing access to kidney transplantation” for all people with kidney failure who could benefit from this treatment, she added.
Dr. Hariharan and Dr. Lentine had no relevant disclosures. Dr. Josephson has been a consultant to UCB and has an ownership interest in Seagen.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Prevalence of youth-onset diabetes climbing, type 2 disease more so in racial/ethnic minorities
The prevalence of youth-onset diabetes in the United States rose significantly from 2001 to 2017, with rates of type 2 diabetes climbing disproportionately among racial/ethnic minorities, according to investigators.
In individuals aged 19 years or younger, prevalence rates of type 1 and type 2 diabetes increased 45.1% and 95.3%, respectively, reported lead author Jean M. Lawrence, ScD, MPH, MSSA, program director of the division of diabetes, endocrinology, and metabolic diseases at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md., and colleagues.
“Elucidating differences in diabetes prevalence trends by diabetes type and demographic characteristics is essential to describe the burden of disease and to estimate current and future resource needs,” Dr. Lawrence and colleagues wrote in JAMA.
The retrospective analysis was a part of the ongoing SEARCH study, which includes data from individuals in six areas across the United States: Colorado, California, Ohio, South Carolina, Washington state, and Arizona/New Mexico (Indian Health Services). In the present report, three prevalence years were evaluated: 2001, 2009, and 2017. For each year, approximately 3.5 million youths were included. Findings were reported in terms of diabetes type, race/ethnicity, age at diagnosis, and sex.
Absolute prevalence of type 1 diabetes per 1,000 youths increased from 1.48 in 2001, to 1.93 in 2009, and finally 2.15 in 2017. Across the 16-year period, this represents an absolute increase of 0.67 (95% confidence interval, 0.64-0.70), and a relative increase of 45.1% (95% CI, 40.0%-50.4%). In absolute terms, prevalence increased most among non-Hispanic White (0.93 per 1,000) and non-Hispanic Black (0.89 per 1,000) youths.
While type 2 diabetes was comparatively less common than type 1 diabetes, absolute prevalence per 1,000 youths increased to a greater degree, rising from 0.34 in 2001 to 0.46 in 2009 and to 0.67 in 2017. This amounts to relative increase across the period of 95.3% (95% CI, 77.0%-115.4%). Absolute increases were disproportionate among racial/ethnic minorities, particularly Black and Hispanic youths, who had absolute increases per 1,000 youths of 0.85 (95% CI, 0.74-0.97) and 0.57 (95% CI, 0.51-0.64), respectively, compared with 0.05 (95% CI, 0.03-0.07) for White youths.
“Increases [among Black and Hispanic youths] were not linear,” the investigators noted. “Hispanic youths had a significantly greater increase in the first interval compared with the second interval, while Black youths had no significant increase in the first interval and a significant increase in the second interval.”
Dr. Lawrence and colleagues offered several possible factors driving these trends in type 2 diabetes.
“Changes in anthropometric risk factors appear to play a significant role,” they wrote, noting that “Black and Mexican American teenagers experienced the greatest increase in prevalence of obesity/severe obesity from 1999 to 2018, which may contribute to race and ethnicity differences. Other contributing factors may include increases in exposure to maternal obesity and diabetes (gestational and type 2 diabetes) and exposure to environmental chemicals.”
According to Megan Kelsey, MD, associate professor of pediatric endocrinology, director of lifestyle medicine endocrinology, and medical director of the bariatric surgery center at Children’s Hospital Colorado, Aurora, the increased rates of type 2 diabetes reported by the study are alarming, yet they pale in comparison with what’s been happening since the pandemic began.
“Individual institutions have reported anywhere between a 50% – which is basically what we’re seeing at our hospital – to a 300% increase in new diagnoses [of type 2 diabetes] in a single-year time period,” Dr. Kelsey said in an interview. “So what is reported [in the present study] doesn’t even get at what’s been going on over the past year and a half.”
Dr. Kelsey offered some speculative drivers of this recent surge in cases, including stress, weight gain caused by sedentary behavior and more access to food, and the possibility that SARS-CoV-2 may infect pancreatic islet beta cells, thereby interfering with insulin production.
Type 2 diabetes is particularly concerning among young people, Dr. Kelsey noted, as it is more challenging to manage than adult-onset disease.
Young patients “also develop complications much sooner than you’d expect,” she added. “So we really need to understand why these rates are increasing, how we can identify kids at risk, and how we can better prevent it, so we aren’t stuck with a disease that’s really difficult to treat.”
To this end, the NIH recently opened applications for investigators to participate in a prospective longitudinal study of youth-onset type 2 diabetes. Young people at risk of diabetes will be followed through puberty, a period of increased risk, according to Dr. Kelsey.
“The goal will be to take kids who don’t yet have [type 2] diabetes, but are at risk, and try to better understand, as some of them progress to developing diabetes, what is going on,” Dr. Kelsey said. “What are other factors that we can use to better predict who’s going to develop diabetes? And can we use the information from this [upcoming] study to understand how to better prevent it? Because nothing that has been tried so far has worked.”
The study was supported by the Centers for Disease Control and Prevention, NIDDK, and others. The investigators and Dr. Kelsey reported no conflicts of interest.
The prevalence of youth-onset diabetes in the United States rose significantly from 2001 to 2017, with rates of type 2 diabetes climbing disproportionately among racial/ethnic minorities, according to investigators.
In individuals aged 19 years or younger, prevalence rates of type 1 and type 2 diabetes increased 45.1% and 95.3%, respectively, reported lead author Jean M. Lawrence, ScD, MPH, MSSA, program director of the division of diabetes, endocrinology, and metabolic diseases at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md., and colleagues.
“Elucidating differences in diabetes prevalence trends by diabetes type and demographic characteristics is essential to describe the burden of disease and to estimate current and future resource needs,” Dr. Lawrence and colleagues wrote in JAMA.
The retrospective analysis was a part of the ongoing SEARCH study, which includes data from individuals in six areas across the United States: Colorado, California, Ohio, South Carolina, Washington state, and Arizona/New Mexico (Indian Health Services). In the present report, three prevalence years were evaluated: 2001, 2009, and 2017. For each year, approximately 3.5 million youths were included. Findings were reported in terms of diabetes type, race/ethnicity, age at diagnosis, and sex.
Absolute prevalence of type 1 diabetes per 1,000 youths increased from 1.48 in 2001, to 1.93 in 2009, and finally 2.15 in 2017. Across the 16-year period, this represents an absolute increase of 0.67 (95% confidence interval, 0.64-0.70), and a relative increase of 45.1% (95% CI, 40.0%-50.4%). In absolute terms, prevalence increased most among non-Hispanic White (0.93 per 1,000) and non-Hispanic Black (0.89 per 1,000) youths.
While type 2 diabetes was comparatively less common than type 1 diabetes, absolute prevalence per 1,000 youths increased to a greater degree, rising from 0.34 in 2001 to 0.46 in 2009 and to 0.67 in 2017. This amounts to relative increase across the period of 95.3% (95% CI, 77.0%-115.4%). Absolute increases were disproportionate among racial/ethnic minorities, particularly Black and Hispanic youths, who had absolute increases per 1,000 youths of 0.85 (95% CI, 0.74-0.97) and 0.57 (95% CI, 0.51-0.64), respectively, compared with 0.05 (95% CI, 0.03-0.07) for White youths.
“Increases [among Black and Hispanic youths] were not linear,” the investigators noted. “Hispanic youths had a significantly greater increase in the first interval compared with the second interval, while Black youths had no significant increase in the first interval and a significant increase in the second interval.”
Dr. Lawrence and colleagues offered several possible factors driving these trends in type 2 diabetes.
“Changes in anthropometric risk factors appear to play a significant role,” they wrote, noting that “Black and Mexican American teenagers experienced the greatest increase in prevalence of obesity/severe obesity from 1999 to 2018, which may contribute to race and ethnicity differences. Other contributing factors may include increases in exposure to maternal obesity and diabetes (gestational and type 2 diabetes) and exposure to environmental chemicals.”
According to Megan Kelsey, MD, associate professor of pediatric endocrinology, director of lifestyle medicine endocrinology, and medical director of the bariatric surgery center at Children’s Hospital Colorado, Aurora, the increased rates of type 2 diabetes reported by the study are alarming, yet they pale in comparison with what’s been happening since the pandemic began.
“Individual institutions have reported anywhere between a 50% – which is basically what we’re seeing at our hospital – to a 300% increase in new diagnoses [of type 2 diabetes] in a single-year time period,” Dr. Kelsey said in an interview. “So what is reported [in the present study] doesn’t even get at what’s been going on over the past year and a half.”
Dr. Kelsey offered some speculative drivers of this recent surge in cases, including stress, weight gain caused by sedentary behavior and more access to food, and the possibility that SARS-CoV-2 may infect pancreatic islet beta cells, thereby interfering with insulin production.
Type 2 diabetes is particularly concerning among young people, Dr. Kelsey noted, as it is more challenging to manage than adult-onset disease.
Young patients “also develop complications much sooner than you’d expect,” she added. “So we really need to understand why these rates are increasing, how we can identify kids at risk, and how we can better prevent it, so we aren’t stuck with a disease that’s really difficult to treat.”
To this end, the NIH recently opened applications for investigators to participate in a prospective longitudinal study of youth-onset type 2 diabetes. Young people at risk of diabetes will be followed through puberty, a period of increased risk, according to Dr. Kelsey.
“The goal will be to take kids who don’t yet have [type 2] diabetes, but are at risk, and try to better understand, as some of them progress to developing diabetes, what is going on,” Dr. Kelsey said. “What are other factors that we can use to better predict who’s going to develop diabetes? And can we use the information from this [upcoming] study to understand how to better prevent it? Because nothing that has been tried so far has worked.”
The study was supported by the Centers for Disease Control and Prevention, NIDDK, and others. The investigators and Dr. Kelsey reported no conflicts of interest.
The prevalence of youth-onset diabetes in the United States rose significantly from 2001 to 2017, with rates of type 2 diabetes climbing disproportionately among racial/ethnic minorities, according to investigators.
In individuals aged 19 years or younger, prevalence rates of type 1 and type 2 diabetes increased 45.1% and 95.3%, respectively, reported lead author Jean M. Lawrence, ScD, MPH, MSSA, program director of the division of diabetes, endocrinology, and metabolic diseases at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md., and colleagues.
“Elucidating differences in diabetes prevalence trends by diabetes type and demographic characteristics is essential to describe the burden of disease and to estimate current and future resource needs,” Dr. Lawrence and colleagues wrote in JAMA.
The retrospective analysis was a part of the ongoing SEARCH study, which includes data from individuals in six areas across the United States: Colorado, California, Ohio, South Carolina, Washington state, and Arizona/New Mexico (Indian Health Services). In the present report, three prevalence years were evaluated: 2001, 2009, and 2017. For each year, approximately 3.5 million youths were included. Findings were reported in terms of diabetes type, race/ethnicity, age at diagnosis, and sex.
Absolute prevalence of type 1 diabetes per 1,000 youths increased from 1.48 in 2001, to 1.93 in 2009, and finally 2.15 in 2017. Across the 16-year period, this represents an absolute increase of 0.67 (95% confidence interval, 0.64-0.70), and a relative increase of 45.1% (95% CI, 40.0%-50.4%). In absolute terms, prevalence increased most among non-Hispanic White (0.93 per 1,000) and non-Hispanic Black (0.89 per 1,000) youths.
While type 2 diabetes was comparatively less common than type 1 diabetes, absolute prevalence per 1,000 youths increased to a greater degree, rising from 0.34 in 2001 to 0.46 in 2009 and to 0.67 in 2017. This amounts to relative increase across the period of 95.3% (95% CI, 77.0%-115.4%). Absolute increases were disproportionate among racial/ethnic minorities, particularly Black and Hispanic youths, who had absolute increases per 1,000 youths of 0.85 (95% CI, 0.74-0.97) and 0.57 (95% CI, 0.51-0.64), respectively, compared with 0.05 (95% CI, 0.03-0.07) for White youths.
“Increases [among Black and Hispanic youths] were not linear,” the investigators noted. “Hispanic youths had a significantly greater increase in the first interval compared with the second interval, while Black youths had no significant increase in the first interval and a significant increase in the second interval.”
Dr. Lawrence and colleagues offered several possible factors driving these trends in type 2 diabetes.
“Changes in anthropometric risk factors appear to play a significant role,” they wrote, noting that “Black and Mexican American teenagers experienced the greatest increase in prevalence of obesity/severe obesity from 1999 to 2018, which may contribute to race and ethnicity differences. Other contributing factors may include increases in exposure to maternal obesity and diabetes (gestational and type 2 diabetes) and exposure to environmental chemicals.”
According to Megan Kelsey, MD, associate professor of pediatric endocrinology, director of lifestyle medicine endocrinology, and medical director of the bariatric surgery center at Children’s Hospital Colorado, Aurora, the increased rates of type 2 diabetes reported by the study are alarming, yet they pale in comparison with what’s been happening since the pandemic began.
“Individual institutions have reported anywhere between a 50% – which is basically what we’re seeing at our hospital – to a 300% increase in new diagnoses [of type 2 diabetes] in a single-year time period,” Dr. Kelsey said in an interview. “So what is reported [in the present study] doesn’t even get at what’s been going on over the past year and a half.”
Dr. Kelsey offered some speculative drivers of this recent surge in cases, including stress, weight gain caused by sedentary behavior and more access to food, and the possibility that SARS-CoV-2 may infect pancreatic islet beta cells, thereby interfering with insulin production.
Type 2 diabetes is particularly concerning among young people, Dr. Kelsey noted, as it is more challenging to manage than adult-onset disease.
Young patients “also develop complications much sooner than you’d expect,” she added. “So we really need to understand why these rates are increasing, how we can identify kids at risk, and how we can better prevent it, so we aren’t stuck with a disease that’s really difficult to treat.”
To this end, the NIH recently opened applications for investigators to participate in a prospective longitudinal study of youth-onset type 2 diabetes. Young people at risk of diabetes will be followed through puberty, a period of increased risk, according to Dr. Kelsey.
“The goal will be to take kids who don’t yet have [type 2] diabetes, but are at risk, and try to better understand, as some of them progress to developing diabetes, what is going on,” Dr. Kelsey said. “What are other factors that we can use to better predict who’s going to develop diabetes? And can we use the information from this [upcoming] study to understand how to better prevent it? Because nothing that has been tried so far has worked.”
The study was supported by the Centers for Disease Control and Prevention, NIDDK, and others. The investigators and Dr. Kelsey reported no conflicts of interest.
FROM JAMA
US Preventive Services Task Force lowers diabetes screening age for overweight
The United States Preventive Services Task Force has updated its recommendation on the age of screening for prediabetes and type 2 diabetes in the primary care setting – lowering the age from 40 to 35 years for asymptomatic patients who are overweight or obese and encouraging greater interventions when patients do show a risk.
“The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit,” the task force concludes in its recommendation, published Aug. 24 in JAMA.
“Clinicians should offer or refer patients with prediabetes to effective preventive interventions,” they write.
Experts commenting on the issue strongly emphasize that it’s not just the screening, but the subsequent intervention that is needed to make a difference.
“If young adults newly identified with abnormal glucose metabolism do not receive the needed intensive behavioral change support, screening may provide no benefit,” write Richard W. Grant, MD, MPH, and colleagues in an editorial published with the recommendation.
“Given the role of our obesogenic and physically inactive society in the shift toward earlier onset of diabetes, efforts to increase screening and recognition of abnormal glucose metabolism must be coupled with robust public health measures to address the underlying contributors.”
BMI cutoff lower for at-risk ethnic populations
The recommendation, which updates the task force’s 2015 guideline, carries a “B” classification, meaning the USPSTF has high certainty that the net benefit is moderate. It now specifies screening from age 35to 70 for persons classified as overweight (body mass index at least 25) or obese (BMI at least 30) and recommends referral to preventive interventions when patients are found to have prediabetes.
In addition to recommendations of lifestyle changes, such as diet and physical activity, the task force also endorses the diabetes drug metformin as a beneficial intervention in the prevention or delay of diabetes, while noting fewer overall health benefits from metformin than from the lifestyle changes.
A lower BMI cutoff of at least 23 is recommended for diabetes screening of Asian Americans, and, importantly, screening for prediabetes and diabetes should be considered at an even earlier age if the patient is from a population with a disproportionately high prevalence of diabetes, including American Indian/Alaska Native, Black, Hawaiian/Pacific Islander, Hispanic/Latino, the task force recommends.
Screening tests should include fasting plasma glucose, hemoglobin A1c, or an oral glucose tolerance test. Although screening every 3 years “may be a reasonable approach for adults with normal blood glucose levels,” the task force adds that “the optimal screening interval for adults with an initial normal glucose test result is uncertain.”
Data review: Few with prediabetes know they have it
The need for the update was prompted by troubling data showing increasing diabetes rates despite early signs that can and should be identified and acted upon in the primary care setting to prevent disease progression.
Data from the Centers for Disease Control and Prevention, for instance, show that while 13% of all U.S. adults 18 years or older have diabetes and 35% meet criteria for prediabetes, as many as 21% of those with diabetes were not aware of or did not report having the disease. Furthermore, only a small fraction – 15% of those with prediabetes – said they had been told by a health professional that they had this condition, the task force notes.
The task force’s final recommendation was based on a systematic review of evidence regarding the screening of asymptomatic, nonpregnant adults and the harms and benefits of interventions, such as physical activity, behavioral counseling, or pharmacotherapy.
Among key evidence supporting the lower age was a 2014 study showing that the number of people necessary to obtain one positive test for diabetes with screening sharply drops from 80 among those aged 30-34 years to just 31 among those aged 36-39.
Opportunistic universal screening of eligible people aged 35 and older would yield a ratio of 1 out of just 15 to spot a positive test, the authors of that study reported.
In addition, a large cohort study in more than 77,000 people with prediabetes strongly links the risk of developing diabetes with increases in A1c level and with increasing BMI.
ADA recommendations differ
The new recommendations differ from American Diabetes Association guidelines, which call for diabetes screening at all ages for people who are overweight or obese and who have one or more risk factors, such as physical inactivity or a first-degree relative with diabetes. If results are normal, repeat screening at least every 3 years is recommended.
The ADA further recommends universal screening for all adults 45 years and older, regardless of their risk factors.
For the screening of adults over 45, the ADA recommends using a fasting plasma glucose level, 2-hour plasma glucose level during a 75-g oral glucose tolerance test, or A1c level, regardless of risk factors.
The American Association of Clinical Endocrinology also recommends universal screening for prediabetes and diabetes for all adults 45 years or older, regardless of risk factors, and also advises screening those who have risk factors for diabetes regardless of age.
Screening of little benefit without behavior change support
In an interview, Dr. Grant added that broad efforts are essential as those at the practice level have clearly not succeeded.
“The medical model of individual counseling and referral has not really been effective, and so we really need to think in terms of large-scale public health action,” said Dr. Grant, of the division of research, Kaiser Permanente Northern California, Oakland.
His editorial details the sweeping, multifactorial efforts that are needed.
“To turn this recommendation into action – that is, to translate screening activities into improved clinical outcomes – change is needed at the patient-clinician level (recognizing and encouraging eligible individuals to be screened), health care system level (reducing screening barriers and ensuring access to robust lifestyle programs), and societal level (applying effective public health interventions to reduce obesity and increase exercise),” they write.
A top priority has to be a focus on individuals of diverse backgrounds and issues such as access to healthy programs in minority communities, Dr. Grant noted.
“Newly diagnosed adults are more likely to be African-American and Latinx,” he said.
“We really need to invest in healthier communities for low-income, non-White communities to reverse the persistent health care disparities in these communities.”
While the challenges may appear daunting, history shows they are not necessarily insurmountable – as evidenced in the campaign to discourage tobacco smoking.
“National smoking cessation efforts are one example of a mostly successful public health campaign that has made a difference in health behaviors,” Grant noted.
The recommendation is also posted on the USPSTF web site .
Dr. Grant reports receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute.
The United States Preventive Services Task Force has updated its recommendation on the age of screening for prediabetes and type 2 diabetes in the primary care setting – lowering the age from 40 to 35 years for asymptomatic patients who are overweight or obese and encouraging greater interventions when patients do show a risk.
“The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit,” the task force concludes in its recommendation, published Aug. 24 in JAMA.
“Clinicians should offer or refer patients with prediabetes to effective preventive interventions,” they write.
Experts commenting on the issue strongly emphasize that it’s not just the screening, but the subsequent intervention that is needed to make a difference.
“If young adults newly identified with abnormal glucose metabolism do not receive the needed intensive behavioral change support, screening may provide no benefit,” write Richard W. Grant, MD, MPH, and colleagues in an editorial published with the recommendation.
“Given the role of our obesogenic and physically inactive society in the shift toward earlier onset of diabetes, efforts to increase screening and recognition of abnormal glucose metabolism must be coupled with robust public health measures to address the underlying contributors.”
BMI cutoff lower for at-risk ethnic populations
The recommendation, which updates the task force’s 2015 guideline, carries a “B” classification, meaning the USPSTF has high certainty that the net benefit is moderate. It now specifies screening from age 35to 70 for persons classified as overweight (body mass index at least 25) or obese (BMI at least 30) and recommends referral to preventive interventions when patients are found to have prediabetes.
In addition to recommendations of lifestyle changes, such as diet and physical activity, the task force also endorses the diabetes drug metformin as a beneficial intervention in the prevention or delay of diabetes, while noting fewer overall health benefits from metformin than from the lifestyle changes.
A lower BMI cutoff of at least 23 is recommended for diabetes screening of Asian Americans, and, importantly, screening for prediabetes and diabetes should be considered at an even earlier age if the patient is from a population with a disproportionately high prevalence of diabetes, including American Indian/Alaska Native, Black, Hawaiian/Pacific Islander, Hispanic/Latino, the task force recommends.
Screening tests should include fasting plasma glucose, hemoglobin A1c, or an oral glucose tolerance test. Although screening every 3 years “may be a reasonable approach for adults with normal blood glucose levels,” the task force adds that “the optimal screening interval for adults with an initial normal glucose test result is uncertain.”
Data review: Few with prediabetes know they have it
The need for the update was prompted by troubling data showing increasing diabetes rates despite early signs that can and should be identified and acted upon in the primary care setting to prevent disease progression.
Data from the Centers for Disease Control and Prevention, for instance, show that while 13% of all U.S. adults 18 years or older have diabetes and 35% meet criteria for prediabetes, as many as 21% of those with diabetes were not aware of or did not report having the disease. Furthermore, only a small fraction – 15% of those with prediabetes – said they had been told by a health professional that they had this condition, the task force notes.
The task force’s final recommendation was based on a systematic review of evidence regarding the screening of asymptomatic, nonpregnant adults and the harms and benefits of interventions, such as physical activity, behavioral counseling, or pharmacotherapy.
Among key evidence supporting the lower age was a 2014 study showing that the number of people necessary to obtain one positive test for diabetes with screening sharply drops from 80 among those aged 30-34 years to just 31 among those aged 36-39.
Opportunistic universal screening of eligible people aged 35 and older would yield a ratio of 1 out of just 15 to spot a positive test, the authors of that study reported.
In addition, a large cohort study in more than 77,000 people with prediabetes strongly links the risk of developing diabetes with increases in A1c level and with increasing BMI.
ADA recommendations differ
The new recommendations differ from American Diabetes Association guidelines, which call for diabetes screening at all ages for people who are overweight or obese and who have one or more risk factors, such as physical inactivity or a first-degree relative with diabetes. If results are normal, repeat screening at least every 3 years is recommended.
The ADA further recommends universal screening for all adults 45 years and older, regardless of their risk factors.
For the screening of adults over 45, the ADA recommends using a fasting plasma glucose level, 2-hour plasma glucose level during a 75-g oral glucose tolerance test, or A1c level, regardless of risk factors.
The American Association of Clinical Endocrinology also recommends universal screening for prediabetes and diabetes for all adults 45 years or older, regardless of risk factors, and also advises screening those who have risk factors for diabetes regardless of age.
Screening of little benefit without behavior change support
In an interview, Dr. Grant added that broad efforts are essential as those at the practice level have clearly not succeeded.
“The medical model of individual counseling and referral has not really been effective, and so we really need to think in terms of large-scale public health action,” said Dr. Grant, of the division of research, Kaiser Permanente Northern California, Oakland.
His editorial details the sweeping, multifactorial efforts that are needed.
“To turn this recommendation into action – that is, to translate screening activities into improved clinical outcomes – change is needed at the patient-clinician level (recognizing and encouraging eligible individuals to be screened), health care system level (reducing screening barriers and ensuring access to robust lifestyle programs), and societal level (applying effective public health interventions to reduce obesity and increase exercise),” they write.
A top priority has to be a focus on individuals of diverse backgrounds and issues such as access to healthy programs in minority communities, Dr. Grant noted.
“Newly diagnosed adults are more likely to be African-American and Latinx,” he said.
“We really need to invest in healthier communities for low-income, non-White communities to reverse the persistent health care disparities in these communities.”
While the challenges may appear daunting, history shows they are not necessarily insurmountable – as evidenced in the campaign to discourage tobacco smoking.
“National smoking cessation efforts are one example of a mostly successful public health campaign that has made a difference in health behaviors,” Grant noted.
The recommendation is also posted on the USPSTF web site .
Dr. Grant reports receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute.
The United States Preventive Services Task Force has updated its recommendation on the age of screening for prediabetes and type 2 diabetes in the primary care setting – lowering the age from 40 to 35 years for asymptomatic patients who are overweight or obese and encouraging greater interventions when patients do show a risk.
“The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit,” the task force concludes in its recommendation, published Aug. 24 in JAMA.
“Clinicians should offer or refer patients with prediabetes to effective preventive interventions,” they write.
Experts commenting on the issue strongly emphasize that it’s not just the screening, but the subsequent intervention that is needed to make a difference.
“If young adults newly identified with abnormal glucose metabolism do not receive the needed intensive behavioral change support, screening may provide no benefit,” write Richard W. Grant, MD, MPH, and colleagues in an editorial published with the recommendation.
“Given the role of our obesogenic and physically inactive society in the shift toward earlier onset of diabetes, efforts to increase screening and recognition of abnormal glucose metabolism must be coupled with robust public health measures to address the underlying contributors.”
BMI cutoff lower for at-risk ethnic populations
The recommendation, which updates the task force’s 2015 guideline, carries a “B” classification, meaning the USPSTF has high certainty that the net benefit is moderate. It now specifies screening from age 35to 70 for persons classified as overweight (body mass index at least 25) or obese (BMI at least 30) and recommends referral to preventive interventions when patients are found to have prediabetes.
In addition to recommendations of lifestyle changes, such as diet and physical activity, the task force also endorses the diabetes drug metformin as a beneficial intervention in the prevention or delay of diabetes, while noting fewer overall health benefits from metformin than from the lifestyle changes.
A lower BMI cutoff of at least 23 is recommended for diabetes screening of Asian Americans, and, importantly, screening for prediabetes and diabetes should be considered at an even earlier age if the patient is from a population with a disproportionately high prevalence of diabetes, including American Indian/Alaska Native, Black, Hawaiian/Pacific Islander, Hispanic/Latino, the task force recommends.
Screening tests should include fasting plasma glucose, hemoglobin A1c, or an oral glucose tolerance test. Although screening every 3 years “may be a reasonable approach for adults with normal blood glucose levels,” the task force adds that “the optimal screening interval for adults with an initial normal glucose test result is uncertain.”
Data review: Few with prediabetes know they have it
The need for the update was prompted by troubling data showing increasing diabetes rates despite early signs that can and should be identified and acted upon in the primary care setting to prevent disease progression.
Data from the Centers for Disease Control and Prevention, for instance, show that while 13% of all U.S. adults 18 years or older have diabetes and 35% meet criteria for prediabetes, as many as 21% of those with diabetes were not aware of or did not report having the disease. Furthermore, only a small fraction – 15% of those with prediabetes – said they had been told by a health professional that they had this condition, the task force notes.
The task force’s final recommendation was based on a systematic review of evidence regarding the screening of asymptomatic, nonpregnant adults and the harms and benefits of interventions, such as physical activity, behavioral counseling, or pharmacotherapy.
Among key evidence supporting the lower age was a 2014 study showing that the number of people necessary to obtain one positive test for diabetes with screening sharply drops from 80 among those aged 30-34 years to just 31 among those aged 36-39.
Opportunistic universal screening of eligible people aged 35 and older would yield a ratio of 1 out of just 15 to spot a positive test, the authors of that study reported.
In addition, a large cohort study in more than 77,000 people with prediabetes strongly links the risk of developing diabetes with increases in A1c level and with increasing BMI.
ADA recommendations differ
The new recommendations differ from American Diabetes Association guidelines, which call for diabetes screening at all ages for people who are overweight or obese and who have one or more risk factors, such as physical inactivity or a first-degree relative with diabetes. If results are normal, repeat screening at least every 3 years is recommended.
The ADA further recommends universal screening for all adults 45 years and older, regardless of their risk factors.
For the screening of adults over 45, the ADA recommends using a fasting plasma glucose level, 2-hour plasma glucose level during a 75-g oral glucose tolerance test, or A1c level, regardless of risk factors.
The American Association of Clinical Endocrinology also recommends universal screening for prediabetes and diabetes for all adults 45 years or older, regardless of risk factors, and also advises screening those who have risk factors for diabetes regardless of age.
Screening of little benefit without behavior change support
In an interview, Dr. Grant added that broad efforts are essential as those at the practice level have clearly not succeeded.
“The medical model of individual counseling and referral has not really been effective, and so we really need to think in terms of large-scale public health action,” said Dr. Grant, of the division of research, Kaiser Permanente Northern California, Oakland.
His editorial details the sweeping, multifactorial efforts that are needed.
“To turn this recommendation into action – that is, to translate screening activities into improved clinical outcomes – change is needed at the patient-clinician level (recognizing and encouraging eligible individuals to be screened), health care system level (reducing screening barriers and ensuring access to robust lifestyle programs), and societal level (applying effective public health interventions to reduce obesity and increase exercise),” they write.
A top priority has to be a focus on individuals of diverse backgrounds and issues such as access to healthy programs in minority communities, Dr. Grant noted.
“Newly diagnosed adults are more likely to be African-American and Latinx,” he said.
“We really need to invest in healthier communities for low-income, non-White communities to reverse the persistent health care disparities in these communities.”
While the challenges may appear daunting, history shows they are not necessarily insurmountable – as evidenced in the campaign to discourage tobacco smoking.
“National smoking cessation efforts are one example of a mostly successful public health campaign that has made a difference in health behaviors,” Grant noted.
The recommendation is also posted on the USPSTF web site .
Dr. Grant reports receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute.
FROM JAMA
Family physician Joseph E. Scherger champions lifestyle change
Joseph E. Scherger, MD, MPH, is a family physician of 40 years and an avid runner who has carried over his passion for fitness and nutrition into treating patients.
He achieved this through moving to practicing functional medicine a decade ago.
According to Dr. Scherger, functional medicine “shifts the whole approach [to family medicine], recognizing that people’s chronic diseases, like hypertension and diabetes, are completely reversible, and the reason why is because they’re caused by what we eat and how we live.”
Practicing functional medicine continues to make working exciting for Dr. Scherger, he says.
“Now that I’ve shifted into nutrition and lifestyle, I feel like I’m a healer, you know? I’m not just refilling prescriptions anymore,” he said.
The burden of disease brought about by bad nutrition and our profit-hungry food industry is staggering, explained Dr. Scherger, As such, he encourages his patients to adopt lifestyle and nutritional changes that allow the body to become healthy again.
Dr. Scherger’s shift into lifestyle-oriented medicine reflects his own experiences with healthy living, and how it has impacted his life.
“I’m 70 years old, and I’m still running, and I feel the same as when I was 40 or 50.” He has completed 40 marathons, ten 50K and five 50-mile ultramarathon trail runs, and, although retired from long-distance running, he is currently training for an upcoming 5K Thanksgiving turkey trot with his 6-year-old grandson. “He loves it. He’s faster than I am, I have trouble keeping up with him,” he confessed.
Earlier days of career
“I’ve been very blessed to have a career that kept changing every 5-10 years,” he said. “I’ve been able to evolve in a way of shifting my interests from one area to another,” he said.
Dr. Scherger has held many positions in the medical field, from serving in the National Health Service Corps in Dixon, Calif., as a migrant health physician during 1978-1980, to being chair of graduate medical education at Eisenhower Medical Center in Rancho Mirage, Calif., from 2009 to 2015. In between, he taught at the University of California, Davis, and served as founding dean of the Florida State University College of Medicine.
Originally from Ohio, Dr. Scherger was born in 1950 in the small town of Delphos. He graduated from the University of Dayton in 1971 before attending medical school at University of California, Los Angeles, for 4 years. He then completed a family medicine residency and a masters in public health at the University of Washington, Seattle, in 1978.
A resident of the Golden State for 50 years now, Dr. Scherger describes himself as a “true Californian.” Currently, he is in practice at Eisenhower Health in La Quinta, Calif., where he is a core faculty member in the family medicine residency program. He is also a physician under the health center’s Primary Care 365 program, which offers patients regular communication with and increased access to their physicians, emphasizing on telemedicine. He also founded Restore Health – Disease Reversal, a wellness center in Indian Wells, Calif., that focuses on improving patients’ health through changes in nutrition and lifestyle.
Within his medical practice, Dr. Scherger is seen by colleagues as a doctor who not only advocates for his patients, but also goes above and beyond to solve their problems.
“He’s a leader, an advocate, and he inspires others to do what they do,” said Julia L. Martin, MD, a fellow family medicine practitioner who has been working with Dr. Scherger at the Eisenhower Medical Center for the past 5 years. “Being a physician is a very challenging role. You need to be patient and understanding in trying to investigate what the patient wants and work through that to try to find the solution. Dr. Scherger is really good at that.”
Inspiration for writing
Apart from his roles as a physician and faculty member, Dr. Scherger is also an author of two books: “40 Years in Family Medicine” (Scotts Valley, Calif.: CreateSpace, 2014) and “Lean and Fit: A Doctor’s Journey to Healthy Nutrition and Greater Wellness” (Scotts Valley, Calif.: CreateSpace, 2015). He admits to not being a naturally gifted writer, and is more intrinsically skilled at speaking. When he was in medical school, however, a mentor told him that the written word is eternal, and this left a deep impression on him.
“When I think of something that’s worth writing about, that I think will be a contribution to my field, I don’t hesitate to begin to write and develop,” said Dr. Scherger. “ I’ve done some research that I’m proud of, but most of [my writings] are hopefully thoughtful essays to help move my field along, and it’s enormously satisfying to make these contributions.”
Awards and other contributions to family medicine
Dr. Scherger’s contributions to the field of family medicine have been recognized continuously over his career.
He has served on the board of directors of the American Academy of Family Physicians and the American Board of Family Medicine. He is also the recipient of numerous awards, such as being chosen as Family Physician of the Year by the American Academy of Family Physicians and the California Academy of Family Physicians in 1989. From 1988 to 1991, he was a fellow in the Kellogg National Fellowship Program.
While he has managed to reinvent his own practice and medical focus, Dr. Scherger is also concerned with the need to remodel the current state of primary care and family medicine. Regarding challenges facing the field, he mentions the burnout faced by many doctors.
Nowadays, the work of family medicine includes much more than those common acute illnesses – it includes preventive medicine, chronic illness management and mental health counseling. “Yet, somehow, the whole economic and schedule model is based on brief visits,” said Dr. Scherger. “I think the most common reason that a lot of family doctors are burned out is that they’re expected to see so many people a day, and they know they don’t have enough time to do a really good job.”
He elaborated: “The real challenge now for family practice is to be re-engineered to be for the modern age, and not be still stuck in a ‘make an appointment, come and get it’ model of care, which is outdated. So I’ve been working a long time in trying to reinvent primary care. And, you know, it’s hard to make those changes, and it’s still a work in progress.”
One of the ways Dr. Scherger has been working on the primary care model is to help redesign it for the computer age. He started doing telemedicine and online care in 1997, even though other doctors gave him pushback for doing so at the time. Today, in his practice, half of his patients are remote, and under Eisenhower’s Primary Care 365 service, he uses telemedicine to its fullest potential.
Dr. Martin calls Dr. Scherger an “innovator,” adding: “He really tries to find what works for a solution, in different ways – not just one cookie cutter way.”
Despite nearly 50 years of being a doctor, the profession has not gotten any less rewarding for Dr. Scherger, who says he does not intend to retire as long as he is any good at it.
“My mother always said, ‘Joe, your life should be dedicated to making the world a better place.’ I really took that to heart and realized that my greatest joy is to help other people.”
Joseph E. Scherger, MD, MPH, is a family physician of 40 years and an avid runner who has carried over his passion for fitness and nutrition into treating patients.
He achieved this through moving to practicing functional medicine a decade ago.
According to Dr. Scherger, functional medicine “shifts the whole approach [to family medicine], recognizing that people’s chronic diseases, like hypertension and diabetes, are completely reversible, and the reason why is because they’re caused by what we eat and how we live.”
Practicing functional medicine continues to make working exciting for Dr. Scherger, he says.
“Now that I’ve shifted into nutrition and lifestyle, I feel like I’m a healer, you know? I’m not just refilling prescriptions anymore,” he said.
The burden of disease brought about by bad nutrition and our profit-hungry food industry is staggering, explained Dr. Scherger, As such, he encourages his patients to adopt lifestyle and nutritional changes that allow the body to become healthy again.
Dr. Scherger’s shift into lifestyle-oriented medicine reflects his own experiences with healthy living, and how it has impacted his life.
“I’m 70 years old, and I’m still running, and I feel the same as when I was 40 or 50.” He has completed 40 marathons, ten 50K and five 50-mile ultramarathon trail runs, and, although retired from long-distance running, he is currently training for an upcoming 5K Thanksgiving turkey trot with his 6-year-old grandson. “He loves it. He’s faster than I am, I have trouble keeping up with him,” he confessed.
Earlier days of career
“I’ve been very blessed to have a career that kept changing every 5-10 years,” he said. “I’ve been able to evolve in a way of shifting my interests from one area to another,” he said.
Dr. Scherger has held many positions in the medical field, from serving in the National Health Service Corps in Dixon, Calif., as a migrant health physician during 1978-1980, to being chair of graduate medical education at Eisenhower Medical Center in Rancho Mirage, Calif., from 2009 to 2015. In between, he taught at the University of California, Davis, and served as founding dean of the Florida State University College of Medicine.
Originally from Ohio, Dr. Scherger was born in 1950 in the small town of Delphos. He graduated from the University of Dayton in 1971 before attending medical school at University of California, Los Angeles, for 4 years. He then completed a family medicine residency and a masters in public health at the University of Washington, Seattle, in 1978.
A resident of the Golden State for 50 years now, Dr. Scherger describes himself as a “true Californian.” Currently, he is in practice at Eisenhower Health in La Quinta, Calif., where he is a core faculty member in the family medicine residency program. He is also a physician under the health center’s Primary Care 365 program, which offers patients regular communication with and increased access to their physicians, emphasizing on telemedicine. He also founded Restore Health – Disease Reversal, a wellness center in Indian Wells, Calif., that focuses on improving patients’ health through changes in nutrition and lifestyle.
Within his medical practice, Dr. Scherger is seen by colleagues as a doctor who not only advocates for his patients, but also goes above and beyond to solve their problems.
“He’s a leader, an advocate, and he inspires others to do what they do,” said Julia L. Martin, MD, a fellow family medicine practitioner who has been working with Dr. Scherger at the Eisenhower Medical Center for the past 5 years. “Being a physician is a very challenging role. You need to be patient and understanding in trying to investigate what the patient wants and work through that to try to find the solution. Dr. Scherger is really good at that.”
Inspiration for writing
Apart from his roles as a physician and faculty member, Dr. Scherger is also an author of two books: “40 Years in Family Medicine” (Scotts Valley, Calif.: CreateSpace, 2014) and “Lean and Fit: A Doctor’s Journey to Healthy Nutrition and Greater Wellness” (Scotts Valley, Calif.: CreateSpace, 2015). He admits to not being a naturally gifted writer, and is more intrinsically skilled at speaking. When he was in medical school, however, a mentor told him that the written word is eternal, and this left a deep impression on him.
“When I think of something that’s worth writing about, that I think will be a contribution to my field, I don’t hesitate to begin to write and develop,” said Dr. Scherger. “ I’ve done some research that I’m proud of, but most of [my writings] are hopefully thoughtful essays to help move my field along, and it’s enormously satisfying to make these contributions.”
Awards and other contributions to family medicine
Dr. Scherger’s contributions to the field of family medicine have been recognized continuously over his career.
He has served on the board of directors of the American Academy of Family Physicians and the American Board of Family Medicine. He is also the recipient of numerous awards, such as being chosen as Family Physician of the Year by the American Academy of Family Physicians and the California Academy of Family Physicians in 1989. From 1988 to 1991, he was a fellow in the Kellogg National Fellowship Program.
While he has managed to reinvent his own practice and medical focus, Dr. Scherger is also concerned with the need to remodel the current state of primary care and family medicine. Regarding challenges facing the field, he mentions the burnout faced by many doctors.
Nowadays, the work of family medicine includes much more than those common acute illnesses – it includes preventive medicine, chronic illness management and mental health counseling. “Yet, somehow, the whole economic and schedule model is based on brief visits,” said Dr. Scherger. “I think the most common reason that a lot of family doctors are burned out is that they’re expected to see so many people a day, and they know they don’t have enough time to do a really good job.”
He elaborated: “The real challenge now for family practice is to be re-engineered to be for the modern age, and not be still stuck in a ‘make an appointment, come and get it’ model of care, which is outdated. So I’ve been working a long time in trying to reinvent primary care. And, you know, it’s hard to make those changes, and it’s still a work in progress.”
One of the ways Dr. Scherger has been working on the primary care model is to help redesign it for the computer age. He started doing telemedicine and online care in 1997, even though other doctors gave him pushback for doing so at the time. Today, in his practice, half of his patients are remote, and under Eisenhower’s Primary Care 365 service, he uses telemedicine to its fullest potential.
Dr. Martin calls Dr. Scherger an “innovator,” adding: “He really tries to find what works for a solution, in different ways – not just one cookie cutter way.”
Despite nearly 50 years of being a doctor, the profession has not gotten any less rewarding for Dr. Scherger, who says he does not intend to retire as long as he is any good at it.
“My mother always said, ‘Joe, your life should be dedicated to making the world a better place.’ I really took that to heart and realized that my greatest joy is to help other people.”
Joseph E. Scherger, MD, MPH, is a family physician of 40 years and an avid runner who has carried over his passion for fitness and nutrition into treating patients.
He achieved this through moving to practicing functional medicine a decade ago.
According to Dr. Scherger, functional medicine “shifts the whole approach [to family medicine], recognizing that people’s chronic diseases, like hypertension and diabetes, are completely reversible, and the reason why is because they’re caused by what we eat and how we live.”
Practicing functional medicine continues to make working exciting for Dr. Scherger, he says.
“Now that I’ve shifted into nutrition and lifestyle, I feel like I’m a healer, you know? I’m not just refilling prescriptions anymore,” he said.
The burden of disease brought about by bad nutrition and our profit-hungry food industry is staggering, explained Dr. Scherger, As such, he encourages his patients to adopt lifestyle and nutritional changes that allow the body to become healthy again.
Dr. Scherger’s shift into lifestyle-oriented medicine reflects his own experiences with healthy living, and how it has impacted his life.
“I’m 70 years old, and I’m still running, and I feel the same as when I was 40 or 50.” He has completed 40 marathons, ten 50K and five 50-mile ultramarathon trail runs, and, although retired from long-distance running, he is currently training for an upcoming 5K Thanksgiving turkey trot with his 6-year-old grandson. “He loves it. He’s faster than I am, I have trouble keeping up with him,” he confessed.
Earlier days of career
“I’ve been very blessed to have a career that kept changing every 5-10 years,” he said. “I’ve been able to evolve in a way of shifting my interests from one area to another,” he said.
Dr. Scherger has held many positions in the medical field, from serving in the National Health Service Corps in Dixon, Calif., as a migrant health physician during 1978-1980, to being chair of graduate medical education at Eisenhower Medical Center in Rancho Mirage, Calif., from 2009 to 2015. In between, he taught at the University of California, Davis, and served as founding dean of the Florida State University College of Medicine.
Originally from Ohio, Dr. Scherger was born in 1950 in the small town of Delphos. He graduated from the University of Dayton in 1971 before attending medical school at University of California, Los Angeles, for 4 years. He then completed a family medicine residency and a masters in public health at the University of Washington, Seattle, in 1978.
A resident of the Golden State for 50 years now, Dr. Scherger describes himself as a “true Californian.” Currently, he is in practice at Eisenhower Health in La Quinta, Calif., where he is a core faculty member in the family medicine residency program. He is also a physician under the health center’s Primary Care 365 program, which offers patients regular communication with and increased access to their physicians, emphasizing on telemedicine. He also founded Restore Health – Disease Reversal, a wellness center in Indian Wells, Calif., that focuses on improving patients’ health through changes in nutrition and lifestyle.
Within his medical practice, Dr. Scherger is seen by colleagues as a doctor who not only advocates for his patients, but also goes above and beyond to solve their problems.
“He’s a leader, an advocate, and he inspires others to do what they do,” said Julia L. Martin, MD, a fellow family medicine practitioner who has been working with Dr. Scherger at the Eisenhower Medical Center for the past 5 years. “Being a physician is a very challenging role. You need to be patient and understanding in trying to investigate what the patient wants and work through that to try to find the solution. Dr. Scherger is really good at that.”
Inspiration for writing
Apart from his roles as a physician and faculty member, Dr. Scherger is also an author of two books: “40 Years in Family Medicine” (Scotts Valley, Calif.: CreateSpace, 2014) and “Lean and Fit: A Doctor’s Journey to Healthy Nutrition and Greater Wellness” (Scotts Valley, Calif.: CreateSpace, 2015). He admits to not being a naturally gifted writer, and is more intrinsically skilled at speaking. When he was in medical school, however, a mentor told him that the written word is eternal, and this left a deep impression on him.
“When I think of something that’s worth writing about, that I think will be a contribution to my field, I don’t hesitate to begin to write and develop,” said Dr. Scherger. “ I’ve done some research that I’m proud of, but most of [my writings] are hopefully thoughtful essays to help move my field along, and it’s enormously satisfying to make these contributions.”
Awards and other contributions to family medicine
Dr. Scherger’s contributions to the field of family medicine have been recognized continuously over his career.
He has served on the board of directors of the American Academy of Family Physicians and the American Board of Family Medicine. He is also the recipient of numerous awards, such as being chosen as Family Physician of the Year by the American Academy of Family Physicians and the California Academy of Family Physicians in 1989. From 1988 to 1991, he was a fellow in the Kellogg National Fellowship Program.
While he has managed to reinvent his own practice and medical focus, Dr. Scherger is also concerned with the need to remodel the current state of primary care and family medicine. Regarding challenges facing the field, he mentions the burnout faced by many doctors.
Nowadays, the work of family medicine includes much more than those common acute illnesses – it includes preventive medicine, chronic illness management and mental health counseling. “Yet, somehow, the whole economic and schedule model is based on brief visits,” said Dr. Scherger. “I think the most common reason that a lot of family doctors are burned out is that they’re expected to see so many people a day, and they know they don’t have enough time to do a really good job.”
He elaborated: “The real challenge now for family practice is to be re-engineered to be for the modern age, and not be still stuck in a ‘make an appointment, come and get it’ model of care, which is outdated. So I’ve been working a long time in trying to reinvent primary care. And, you know, it’s hard to make those changes, and it’s still a work in progress.”
One of the ways Dr. Scherger has been working on the primary care model is to help redesign it for the computer age. He started doing telemedicine and online care in 1997, even though other doctors gave him pushback for doing so at the time. Today, in his practice, half of his patients are remote, and under Eisenhower’s Primary Care 365 service, he uses telemedicine to its fullest potential.
Dr. Martin calls Dr. Scherger an “innovator,” adding: “He really tries to find what works for a solution, in different ways – not just one cookie cutter way.”
Despite nearly 50 years of being a doctor, the profession has not gotten any less rewarding for Dr. Scherger, who says he does not intend to retire as long as he is any good at it.
“My mother always said, ‘Joe, your life should be dedicated to making the world a better place.’ I really took that to heart and realized that my greatest joy is to help other people.”
SGLT2 inhibitor use rising in patients with DKD
U.S. prescribing data from 160,000 adults with type 2 diabetes and diabetic kidney disease showed a notable uptick in new prescriptions for sodium-glucose cotransporter 2 inhibitors and less dramatic gains for glucagonlike peptide–1 receptor agonists during 2019 and continuing into early 2020, compared with prior years, with usage levels of both classes during the first quarter of 2020 rivaling those of more traditional agents including metformin and insulin.
During the first 3 months of 2020, initiation of a SGLT2 inhibitor constituted 13% of all new starts of an antidiabetes drug among adults with type 2 diabetes and diabetic kidney disease (DKD). This compared with initiation rates during the same early 2020 period of 17% for GLP-1 receptor agonists, 19% for metformin, 16% for sulfonylureas, 15% for insulins, 14% for thiazolidinediones, and 6% for dipeptidyl peptidase–4 inhibitors, the seven drug classes examined in a study published in Diabetes Care.
Early 2020 was the first time that starts of a GLP-1 receptor agonist ranked second (behind only metformin) among these seven drug classes in the studied U.S. population, and early 2020 also marked an unprecedentedly high start rate for SGLT2 inhibitors that nearly tripled the roughly 5% rate in place as recently as 2018.
Rises are ‘what we expected’
The recent rise of SGLT2 inhibitors and GLP-1 receptor agonists in these patients “was what we expected,” given the evidence for both classes in slowing progression of DKD, said Julie M. Paik, MD, senior author on the study and a nephrologist and pharmacoepidemiologist at Brigham and Women’s Hospital in Boston.
“We’ve seen other beneficial drugs slow on the uptake, so it’s not surprising to see it here, and I’m optimistic” about further increases going forward, she said in an interview.
Both drug classes “were originally marketed as diabetes drugs,” and it is only since 2019, with the publication of trials showing dramatic renal benefits from canagliflozin (Invokana) in CREDENCE, and from dapagliflozin (Farxiga) in DAPA-CKD in 2020 that the evidence became truly compelling for SGLT2 inhibitors. This evidence also led to new renal-protection indications approved by the Food and Drug Administration for canagliflozin and for dapagliflozin, noted Dr. Paik.
Evidence for renal protection also emerged in 2017 for the GLP-1 receptor agonist liraglutide (Victoza) in the LEADER trial, and for dulaglutide (Trulicity) in the AWARD-7 trial, although neither drug has received a renal indication in its labeling.
By 2020, guidelines for managing patients with type 2 diabetes and chronic kidney disease from the influential Kidney Disease: Improving Global Outcomes organization had identified agents from the SGLT2 inhibitor class as top-tier options, along with metformin, for treating these patients, with agents from the GLP-1 receptor agonist class as the top third class to add in patients who require additional glycemic control.
Additional analyses Dr. Paik and associates ran showed how this played out in terms of which specialists prescribed these drugs during the full period studied beginning in 2013. Throughout this roughly 7-year span, about 70% of the prescriptions written for either SGLT2 inhibitors or for GLP-1 receptor agonists were from internal medicine physicians, followed by about 20% written by endocrinologists. Prescriptions from nephrologists, as well as from cardiologists, have hovered at about 5% each, but seem poised to start rising based on the recently added indications and newer treatment recommendations.
“It’s good to see the recent uptick in use since 2019,” Katherine R. Tuttle, MD, commented in an interview. It’s a positive development for U.S. public health, “but we need to do more to disseminate and implement these life-, kidney-, and heart-saving therapies.”
Future use could approach 80% of DKD patients
Dr. Tuttle estimated that “target” levels of use for SGLT2 inhibitors and for GLP-1 receptor agonists “could reasonably approach 80%” for patients with type 2 diabetes and diabetic kidney disease.
“We will likely move to combination therapy” with simultaneous use of agents from both classes in a targeted way using “precision phenotyping based on clinical characteristics, and eventually perhaps by biomarkers, kidney biopsies, or both.” Combined treatment with both an SGLT2 inhibitor and a GLP-1 receptor agonist may be especially suited to patients with type 2 diabetes, atherosclerotic cardiovascular disease, low estimated glomerular filtration rate, and need for better glycemic control and weight loss, a profile that is “pretty typical” in real-world practice, said Dr. Tuttle, a nephrologist and endocrinologist and executive director for research at Providence Healthcare in Spokane, Wash.
Study included patients with commercial or Medicare Advantage coverage
The study used information in an Optum database that included patients enrolled in either commercial or in Medicare Advantage health insurance plans from 2013 to the first quarter of 2020. This included 160,489 adults with type 2 diabetes and DKD who started during that period at least one agent from any of the seven included drug classes.
This focus may have biased the findings because, overall, U.S. coverage of the relatively expensive agents from the SGLT2 inhibitor and GLP-1 receptor agonist classes has often been problematic.
“There are issues of cost, coverage, and access” using these medications, as well as limited data on cost-effectiveness, Dr. Paik acknowledged. Additional issues that have helped generate prescribing lags include concerns about possible adverse effects, low familiarity by providers with these drugs early on, and limited trial experience using them in older patients. The process of clinicians growing more comfortable prescribing these new agents has depended on their “working through the evidence,” she explained.
The FDA’s approval in July 2021 of finerenone (Kerendia) for treating patients with type 2 diabetes and chronic kidney disease threw yet another new variable into the prescribing mix for these patients.
“SGLT2 inhibitors are here to stay as a new standard of care for patients with diabetic kidney disease, but combination with finerenone might be especially useful for patients with diabetic kidney disease and heart failure,” Dr. Tuttle suggested. A new generation of clinical trials will likely soon launch to test these combinations, she predicted.
Dr. Paik had no disclosures. Dr. Tuttle has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Goldfinch Bio, Eli Lilly, and Novo Nordisk.
U.S. prescribing data from 160,000 adults with type 2 diabetes and diabetic kidney disease showed a notable uptick in new prescriptions for sodium-glucose cotransporter 2 inhibitors and less dramatic gains for glucagonlike peptide–1 receptor agonists during 2019 and continuing into early 2020, compared with prior years, with usage levels of both classes during the first quarter of 2020 rivaling those of more traditional agents including metformin and insulin.
During the first 3 months of 2020, initiation of a SGLT2 inhibitor constituted 13% of all new starts of an antidiabetes drug among adults with type 2 diabetes and diabetic kidney disease (DKD). This compared with initiation rates during the same early 2020 period of 17% for GLP-1 receptor agonists, 19% for metformin, 16% for sulfonylureas, 15% for insulins, 14% for thiazolidinediones, and 6% for dipeptidyl peptidase–4 inhibitors, the seven drug classes examined in a study published in Diabetes Care.
Early 2020 was the first time that starts of a GLP-1 receptor agonist ranked second (behind only metformin) among these seven drug classes in the studied U.S. population, and early 2020 also marked an unprecedentedly high start rate for SGLT2 inhibitors that nearly tripled the roughly 5% rate in place as recently as 2018.
Rises are ‘what we expected’
The recent rise of SGLT2 inhibitors and GLP-1 receptor agonists in these patients “was what we expected,” given the evidence for both classes in slowing progression of DKD, said Julie M. Paik, MD, senior author on the study and a nephrologist and pharmacoepidemiologist at Brigham and Women’s Hospital in Boston.
“We’ve seen other beneficial drugs slow on the uptake, so it’s not surprising to see it here, and I’m optimistic” about further increases going forward, she said in an interview.
Both drug classes “were originally marketed as diabetes drugs,” and it is only since 2019, with the publication of trials showing dramatic renal benefits from canagliflozin (Invokana) in CREDENCE, and from dapagliflozin (Farxiga) in DAPA-CKD in 2020 that the evidence became truly compelling for SGLT2 inhibitors. This evidence also led to new renal-protection indications approved by the Food and Drug Administration for canagliflozin and for dapagliflozin, noted Dr. Paik.
Evidence for renal protection also emerged in 2017 for the GLP-1 receptor agonist liraglutide (Victoza) in the LEADER trial, and for dulaglutide (Trulicity) in the AWARD-7 trial, although neither drug has received a renal indication in its labeling.
By 2020, guidelines for managing patients with type 2 diabetes and chronic kidney disease from the influential Kidney Disease: Improving Global Outcomes organization had identified agents from the SGLT2 inhibitor class as top-tier options, along with metformin, for treating these patients, with agents from the GLP-1 receptor agonist class as the top third class to add in patients who require additional glycemic control.
Additional analyses Dr. Paik and associates ran showed how this played out in terms of which specialists prescribed these drugs during the full period studied beginning in 2013. Throughout this roughly 7-year span, about 70% of the prescriptions written for either SGLT2 inhibitors or for GLP-1 receptor agonists were from internal medicine physicians, followed by about 20% written by endocrinologists. Prescriptions from nephrologists, as well as from cardiologists, have hovered at about 5% each, but seem poised to start rising based on the recently added indications and newer treatment recommendations.
“It’s good to see the recent uptick in use since 2019,” Katherine R. Tuttle, MD, commented in an interview. It’s a positive development for U.S. public health, “but we need to do more to disseminate and implement these life-, kidney-, and heart-saving therapies.”
Future use could approach 80% of DKD patients
Dr. Tuttle estimated that “target” levels of use for SGLT2 inhibitors and for GLP-1 receptor agonists “could reasonably approach 80%” for patients with type 2 diabetes and diabetic kidney disease.
“We will likely move to combination therapy” with simultaneous use of agents from both classes in a targeted way using “precision phenotyping based on clinical characteristics, and eventually perhaps by biomarkers, kidney biopsies, or both.” Combined treatment with both an SGLT2 inhibitor and a GLP-1 receptor agonist may be especially suited to patients with type 2 diabetes, atherosclerotic cardiovascular disease, low estimated glomerular filtration rate, and need for better glycemic control and weight loss, a profile that is “pretty typical” in real-world practice, said Dr. Tuttle, a nephrologist and endocrinologist and executive director for research at Providence Healthcare in Spokane, Wash.
Study included patients with commercial or Medicare Advantage coverage
The study used information in an Optum database that included patients enrolled in either commercial or in Medicare Advantage health insurance plans from 2013 to the first quarter of 2020. This included 160,489 adults with type 2 diabetes and DKD who started during that period at least one agent from any of the seven included drug classes.
This focus may have biased the findings because, overall, U.S. coverage of the relatively expensive agents from the SGLT2 inhibitor and GLP-1 receptor agonist classes has often been problematic.
“There are issues of cost, coverage, and access” using these medications, as well as limited data on cost-effectiveness, Dr. Paik acknowledged. Additional issues that have helped generate prescribing lags include concerns about possible adverse effects, low familiarity by providers with these drugs early on, and limited trial experience using them in older patients. The process of clinicians growing more comfortable prescribing these new agents has depended on their “working through the evidence,” she explained.
The FDA’s approval in July 2021 of finerenone (Kerendia) for treating patients with type 2 diabetes and chronic kidney disease threw yet another new variable into the prescribing mix for these patients.
“SGLT2 inhibitors are here to stay as a new standard of care for patients with diabetic kidney disease, but combination with finerenone might be especially useful for patients with diabetic kidney disease and heart failure,” Dr. Tuttle suggested. A new generation of clinical trials will likely soon launch to test these combinations, she predicted.
Dr. Paik had no disclosures. Dr. Tuttle has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Goldfinch Bio, Eli Lilly, and Novo Nordisk.
U.S. prescribing data from 160,000 adults with type 2 diabetes and diabetic kidney disease showed a notable uptick in new prescriptions for sodium-glucose cotransporter 2 inhibitors and less dramatic gains for glucagonlike peptide–1 receptor agonists during 2019 and continuing into early 2020, compared with prior years, with usage levels of both classes during the first quarter of 2020 rivaling those of more traditional agents including metformin and insulin.
During the first 3 months of 2020, initiation of a SGLT2 inhibitor constituted 13% of all new starts of an antidiabetes drug among adults with type 2 diabetes and diabetic kidney disease (DKD). This compared with initiation rates during the same early 2020 period of 17% for GLP-1 receptor agonists, 19% for metformin, 16% for sulfonylureas, 15% for insulins, 14% for thiazolidinediones, and 6% for dipeptidyl peptidase–4 inhibitors, the seven drug classes examined in a study published in Diabetes Care.
Early 2020 was the first time that starts of a GLP-1 receptor agonist ranked second (behind only metformin) among these seven drug classes in the studied U.S. population, and early 2020 also marked an unprecedentedly high start rate for SGLT2 inhibitors that nearly tripled the roughly 5% rate in place as recently as 2018.
Rises are ‘what we expected’
The recent rise of SGLT2 inhibitors and GLP-1 receptor agonists in these patients “was what we expected,” given the evidence for both classes in slowing progression of DKD, said Julie M. Paik, MD, senior author on the study and a nephrologist and pharmacoepidemiologist at Brigham and Women’s Hospital in Boston.
“We’ve seen other beneficial drugs slow on the uptake, so it’s not surprising to see it here, and I’m optimistic” about further increases going forward, she said in an interview.
Both drug classes “were originally marketed as diabetes drugs,” and it is only since 2019, with the publication of trials showing dramatic renal benefits from canagliflozin (Invokana) in CREDENCE, and from dapagliflozin (Farxiga) in DAPA-CKD in 2020 that the evidence became truly compelling for SGLT2 inhibitors. This evidence also led to new renal-protection indications approved by the Food and Drug Administration for canagliflozin and for dapagliflozin, noted Dr. Paik.
Evidence for renal protection also emerged in 2017 for the GLP-1 receptor agonist liraglutide (Victoza) in the LEADER trial, and for dulaglutide (Trulicity) in the AWARD-7 trial, although neither drug has received a renal indication in its labeling.
By 2020, guidelines for managing patients with type 2 diabetes and chronic kidney disease from the influential Kidney Disease: Improving Global Outcomes organization had identified agents from the SGLT2 inhibitor class as top-tier options, along with metformin, for treating these patients, with agents from the GLP-1 receptor agonist class as the top third class to add in patients who require additional glycemic control.
Additional analyses Dr. Paik and associates ran showed how this played out in terms of which specialists prescribed these drugs during the full period studied beginning in 2013. Throughout this roughly 7-year span, about 70% of the prescriptions written for either SGLT2 inhibitors or for GLP-1 receptor agonists were from internal medicine physicians, followed by about 20% written by endocrinologists. Prescriptions from nephrologists, as well as from cardiologists, have hovered at about 5% each, but seem poised to start rising based on the recently added indications and newer treatment recommendations.
“It’s good to see the recent uptick in use since 2019,” Katherine R. Tuttle, MD, commented in an interview. It’s a positive development for U.S. public health, “but we need to do more to disseminate and implement these life-, kidney-, and heart-saving therapies.”
Future use could approach 80% of DKD patients
Dr. Tuttle estimated that “target” levels of use for SGLT2 inhibitors and for GLP-1 receptor agonists “could reasonably approach 80%” for patients with type 2 diabetes and diabetic kidney disease.
“We will likely move to combination therapy” with simultaneous use of agents from both classes in a targeted way using “precision phenotyping based on clinical characteristics, and eventually perhaps by biomarkers, kidney biopsies, or both.” Combined treatment with both an SGLT2 inhibitor and a GLP-1 receptor agonist may be especially suited to patients with type 2 diabetes, atherosclerotic cardiovascular disease, low estimated glomerular filtration rate, and need for better glycemic control and weight loss, a profile that is “pretty typical” in real-world practice, said Dr. Tuttle, a nephrologist and endocrinologist and executive director for research at Providence Healthcare in Spokane, Wash.
Study included patients with commercial or Medicare Advantage coverage
The study used information in an Optum database that included patients enrolled in either commercial or in Medicare Advantage health insurance plans from 2013 to the first quarter of 2020. This included 160,489 adults with type 2 diabetes and DKD who started during that period at least one agent from any of the seven included drug classes.
This focus may have biased the findings because, overall, U.S. coverage of the relatively expensive agents from the SGLT2 inhibitor and GLP-1 receptor agonist classes has often been problematic.
“There are issues of cost, coverage, and access” using these medications, as well as limited data on cost-effectiveness, Dr. Paik acknowledged. Additional issues that have helped generate prescribing lags include concerns about possible adverse effects, low familiarity by providers with these drugs early on, and limited trial experience using them in older patients. The process of clinicians growing more comfortable prescribing these new agents has depended on their “working through the evidence,” she explained.
The FDA’s approval in July 2021 of finerenone (Kerendia) for treating patients with type 2 diabetes and chronic kidney disease threw yet another new variable into the prescribing mix for these patients.
“SGLT2 inhibitors are here to stay as a new standard of care for patients with diabetic kidney disease, but combination with finerenone might be especially useful for patients with diabetic kidney disease and heart failure,” Dr. Tuttle suggested. A new generation of clinical trials will likely soon launch to test these combinations, she predicted.
Dr. Paik had no disclosures. Dr. Tuttle has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Goldfinch Bio, Eli Lilly, and Novo Nordisk.
FROM DIABETES CARE
Mediterranean diet slows progression of atherosclerosis in CHD
For patients with coronary heart disease (CHD), following a Mediterranean diet is more effective in reducing progression of atherosclerosis than following a low-fat diet, according to new data from the CORDIOPREV randomized, controlled trial.
“The current study is, to our knowledge, the first to establish an effective dietary strategy for secondary cardiovascular prevention, reinforcing the fact that the Mediterranean diet rich in extra virgin olive oil (EVOO) could prevent the progression of atherosclerosis,” the study team said.
The data also show that patients with a higher atherosclerotic burden might benefit the most from the Mediterranean diet.
The study was published online Aug. 10, 2021, in Stroke.
Mediterranean or low fat?
“It is well established that lifestyle and dietary habits powerfully affect cardiovascular risk,” study investigator Elena M. Yubero-Serrano, PhD, with Reina Sofia University Hospital/University of Cordoba (Spain), told this news organization.
“The effectiveness of the Mediterranean diet in reducing cardiovascular risk has been seen in primary prevention. However, currently there is no consensus about a recommended dietary model for the secondary prevention of cardiovascular disease,” she said.
The Coronary Diet Intervention With Olive Oil and Cardiovascular Prevention (CORDIOPREV) study is an ongoing prospective study comparing the effects of two healthy diets for secondary prevention of cardiovascular disease (CVD) in 1002 patients.
The comparative effect of the diets in reducing CVD risk, assessed by quantification of intima-media thickness of the common carotid arteries (IMT-CC), is a key secondary endpoint of the study.
During the study, half of the patients follow a Mediterranean diet rich in EVOO, fruit and vegetables, whole grains, fish, and nuts. The other half follow a diet low in fat and rich in complex carbohydrates.
A total of 939 participants (459 in the low-fat diet group and 480 in the Mediterranean diet group) completed IMT-CC evaluation at baseline, and 809 (377 and 432, respectively) completed the IMT-CC evaluation at 5 years; 731 (335 and 396, respectively) did so at 7 years.
The Mediterranean diet significantly decreased IMT-CC both after 5 years (–0.027; P < .001) and after 7 years (–0.031 mm; P < .001), relative to baseline. In contrast, the low-fat diet did not exert any change on IMT-CC after 5 or 7 years, the researchers report.
The higher the IMT-CC at baseline, the greater the reduction in this parameter.
The Mediterranean diet also produced a greater decrease in IMT-CC and carotid plaque maximum height, compared with the low-fat diet throughout follow-up.
There were no between-group differences in carotid plaque numbers during follow-up.
“Our findings, in addition to reinforcing the clinical benefits of the Mediterranean diet, provide a beneficial dietary strategy as a clinical and therapeutic tool that could reduce the high cardiovascular recurrence in the context of secondary prevention,” Dr. Yubero-Serrano said in an interview.
Earlier data from CORDIOPREV showed that, after 1 year of eating a Mediterranean diet, compared with the low-fat diet, endothelial function was improved among patients with CHD, even those with type 2 diabetes, which was associated with a better balance of vascular homeostasis.
The Mediterranean diet may also modulate the lipid profile, particularly by increasing HDL cholesterol levels. The anti-inflammatory capacity of the Mediterranean diet could be another factor that contributes to reducing the progression of atherosclerosis, the researchers say.
Important study
Reached for comment, Alan Rozanski, MD, professor of medicine, Icahn School of Medicine at Mount Sinai and cardiologist at Mount Sinai Morningside, New York, said: “We know very well that lifestyle factors, diet, and exercise in particular are extremely important in promoting health, vitality, and decreasing risk for chronic diseases, including heart attack and stroke.
“But a lot of the studies depend on epidemiological work. Until now, we haven’t had important prospective studies evaluating different kinds of dietary approaches and how they affect carotid intimal thickening assessments that we can do by ultrasound. So having this kind of imaging study which shows that diet can halt progression of atherosclerosis is important,” said Dr. Rozanski.
“Changing one’s diet is extremely important and potentially beneficial in many ways, and being able to say to a patient with atherosclerosis that we have data that shows you can halt the progression of the disease can be extraordinarily encouraging to many patients,” he noted.
“When people have disease, they very often gravitate toward drugs, but continuing to emphasize lifestyle changes in these people is extremely important,” he added.
The CORDIOPREV study was supported by the Fundación Patrimonio Comunal Olivarero. Dr. Yubero-Serrano and Dr. Rozanski disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
For patients with coronary heart disease (CHD), following a Mediterranean diet is more effective in reducing progression of atherosclerosis than following a low-fat diet, according to new data from the CORDIOPREV randomized, controlled trial.
“The current study is, to our knowledge, the first to establish an effective dietary strategy for secondary cardiovascular prevention, reinforcing the fact that the Mediterranean diet rich in extra virgin olive oil (EVOO) could prevent the progression of atherosclerosis,” the study team said.
The data also show that patients with a higher atherosclerotic burden might benefit the most from the Mediterranean diet.
The study was published online Aug. 10, 2021, in Stroke.
Mediterranean or low fat?
“It is well established that lifestyle and dietary habits powerfully affect cardiovascular risk,” study investigator Elena M. Yubero-Serrano, PhD, with Reina Sofia University Hospital/University of Cordoba (Spain), told this news organization.
“The effectiveness of the Mediterranean diet in reducing cardiovascular risk has been seen in primary prevention. However, currently there is no consensus about a recommended dietary model for the secondary prevention of cardiovascular disease,” she said.
The Coronary Diet Intervention With Olive Oil and Cardiovascular Prevention (CORDIOPREV) study is an ongoing prospective study comparing the effects of two healthy diets for secondary prevention of cardiovascular disease (CVD) in 1002 patients.
The comparative effect of the diets in reducing CVD risk, assessed by quantification of intima-media thickness of the common carotid arteries (IMT-CC), is a key secondary endpoint of the study.
During the study, half of the patients follow a Mediterranean diet rich in EVOO, fruit and vegetables, whole grains, fish, and nuts. The other half follow a diet low in fat and rich in complex carbohydrates.
A total of 939 participants (459 in the low-fat diet group and 480 in the Mediterranean diet group) completed IMT-CC evaluation at baseline, and 809 (377 and 432, respectively) completed the IMT-CC evaluation at 5 years; 731 (335 and 396, respectively) did so at 7 years.
The Mediterranean diet significantly decreased IMT-CC both after 5 years (–0.027; P < .001) and after 7 years (–0.031 mm; P < .001), relative to baseline. In contrast, the low-fat diet did not exert any change on IMT-CC after 5 or 7 years, the researchers report.
The higher the IMT-CC at baseline, the greater the reduction in this parameter.
The Mediterranean diet also produced a greater decrease in IMT-CC and carotid plaque maximum height, compared with the low-fat diet throughout follow-up.
There were no between-group differences in carotid plaque numbers during follow-up.
“Our findings, in addition to reinforcing the clinical benefits of the Mediterranean diet, provide a beneficial dietary strategy as a clinical and therapeutic tool that could reduce the high cardiovascular recurrence in the context of secondary prevention,” Dr. Yubero-Serrano said in an interview.
Earlier data from CORDIOPREV showed that, after 1 year of eating a Mediterranean diet, compared with the low-fat diet, endothelial function was improved among patients with CHD, even those with type 2 diabetes, which was associated with a better balance of vascular homeostasis.
The Mediterranean diet may also modulate the lipid profile, particularly by increasing HDL cholesterol levels. The anti-inflammatory capacity of the Mediterranean diet could be another factor that contributes to reducing the progression of atherosclerosis, the researchers say.
Important study
Reached for comment, Alan Rozanski, MD, professor of medicine, Icahn School of Medicine at Mount Sinai and cardiologist at Mount Sinai Morningside, New York, said: “We know very well that lifestyle factors, diet, and exercise in particular are extremely important in promoting health, vitality, and decreasing risk for chronic diseases, including heart attack and stroke.
“But a lot of the studies depend on epidemiological work. Until now, we haven’t had important prospective studies evaluating different kinds of dietary approaches and how they affect carotid intimal thickening assessments that we can do by ultrasound. So having this kind of imaging study which shows that diet can halt progression of atherosclerosis is important,” said Dr. Rozanski.
“Changing one’s diet is extremely important and potentially beneficial in many ways, and being able to say to a patient with atherosclerosis that we have data that shows you can halt the progression of the disease can be extraordinarily encouraging to many patients,” he noted.
“When people have disease, they very often gravitate toward drugs, but continuing to emphasize lifestyle changes in these people is extremely important,” he added.
The CORDIOPREV study was supported by the Fundación Patrimonio Comunal Olivarero. Dr. Yubero-Serrano and Dr. Rozanski disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
For patients with coronary heart disease (CHD), following a Mediterranean diet is more effective in reducing progression of atherosclerosis than following a low-fat diet, according to new data from the CORDIOPREV randomized, controlled trial.
“The current study is, to our knowledge, the first to establish an effective dietary strategy for secondary cardiovascular prevention, reinforcing the fact that the Mediterranean diet rich in extra virgin olive oil (EVOO) could prevent the progression of atherosclerosis,” the study team said.
The data also show that patients with a higher atherosclerotic burden might benefit the most from the Mediterranean diet.
The study was published online Aug. 10, 2021, in Stroke.
Mediterranean or low fat?
“It is well established that lifestyle and dietary habits powerfully affect cardiovascular risk,” study investigator Elena M. Yubero-Serrano, PhD, with Reina Sofia University Hospital/University of Cordoba (Spain), told this news organization.
“The effectiveness of the Mediterranean diet in reducing cardiovascular risk has been seen in primary prevention. However, currently there is no consensus about a recommended dietary model for the secondary prevention of cardiovascular disease,” she said.
The Coronary Diet Intervention With Olive Oil and Cardiovascular Prevention (CORDIOPREV) study is an ongoing prospective study comparing the effects of two healthy diets for secondary prevention of cardiovascular disease (CVD) in 1002 patients.
The comparative effect of the diets in reducing CVD risk, assessed by quantification of intima-media thickness of the common carotid arteries (IMT-CC), is a key secondary endpoint of the study.
During the study, half of the patients follow a Mediterranean diet rich in EVOO, fruit and vegetables, whole grains, fish, and nuts. The other half follow a diet low in fat and rich in complex carbohydrates.
A total of 939 participants (459 in the low-fat diet group and 480 in the Mediterranean diet group) completed IMT-CC evaluation at baseline, and 809 (377 and 432, respectively) completed the IMT-CC evaluation at 5 years; 731 (335 and 396, respectively) did so at 7 years.
The Mediterranean diet significantly decreased IMT-CC both after 5 years (–0.027; P < .001) and after 7 years (–0.031 mm; P < .001), relative to baseline. In contrast, the low-fat diet did not exert any change on IMT-CC after 5 or 7 years, the researchers report.
The higher the IMT-CC at baseline, the greater the reduction in this parameter.
The Mediterranean diet also produced a greater decrease in IMT-CC and carotid plaque maximum height, compared with the low-fat diet throughout follow-up.
There were no between-group differences in carotid plaque numbers during follow-up.
“Our findings, in addition to reinforcing the clinical benefits of the Mediterranean diet, provide a beneficial dietary strategy as a clinical and therapeutic tool that could reduce the high cardiovascular recurrence in the context of secondary prevention,” Dr. Yubero-Serrano said in an interview.
Earlier data from CORDIOPREV showed that, after 1 year of eating a Mediterranean diet, compared with the low-fat diet, endothelial function was improved among patients with CHD, even those with type 2 diabetes, which was associated with a better balance of vascular homeostasis.
The Mediterranean diet may also modulate the lipid profile, particularly by increasing HDL cholesterol levels. The anti-inflammatory capacity of the Mediterranean diet could be another factor that contributes to reducing the progression of atherosclerosis, the researchers say.
Important study
Reached for comment, Alan Rozanski, MD, professor of medicine, Icahn School of Medicine at Mount Sinai and cardiologist at Mount Sinai Morningside, New York, said: “We know very well that lifestyle factors, diet, and exercise in particular are extremely important in promoting health, vitality, and decreasing risk for chronic diseases, including heart attack and stroke.
“But a lot of the studies depend on epidemiological work. Until now, we haven’t had important prospective studies evaluating different kinds of dietary approaches and how they affect carotid intimal thickening assessments that we can do by ultrasound. So having this kind of imaging study which shows that diet can halt progression of atherosclerosis is important,” said Dr. Rozanski.
“Changing one’s diet is extremely important and potentially beneficial in many ways, and being able to say to a patient with atherosclerosis that we have data that shows you can halt the progression of the disease can be extraordinarily encouraging to many patients,” he noted.
“When people have disease, they very often gravitate toward drugs, but continuing to emphasize lifestyle changes in these people is extremely important,” he added.
The CORDIOPREV study was supported by the Fundación Patrimonio Comunal Olivarero. Dr. Yubero-Serrano and Dr. Rozanski disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Empagliflozin gets HFrEF approval from FDA
The U.S. Food and Drug Administration approved empagliflozin (Jardiance) as a treatment for adults with heart failure with reduced ejection fraction (HFrEF) regardless of whether patients have diabetes on Aug. 18, making it the second agent from the sodium-glucose transporter 2 inhibitor class to received this indication.
Empagliflozin first received FDA marketing approval in 2014 for improving glycemic control in patients with type 2 diabetes, and in 2016 the agency added a second indication of reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease. The newly granted indication for patients with HFrEF without regard to glycemic status was for reducing the risk for cardiovascular death and hospitalization for heart failure, according to a statement from Boehringer Ingelheim and Lilly, the two companies that together market empagliflozin.
The statement also said that the approval allowed for empagliflozin treatment in patients with HFrEF and an estimated glomerular filtration rate (eGFR) as low as 20 mL/min per 1.73 m2, in contrast to its indication for improving glycemic control in patients with type 2 diabetes that limits use to patients with an eGFR of at least 30 mL per 1.73 m2.
EMPEROR-Reduced results drive approval
The FDA based its decision on results from the EMPEROR-Reduced study, first reported in August 2020, that showed treatment of patients with HFrEF with empagliflozin on top of standard therapy for a median of 16 months cut the incidence of cardiovascular death or hospitalization for worsening heart failure by 25% relative to placebo, and by an absolute 5.3%, compared with placebo-treated patients.
Patients enrolled in EMPEROR-Reduced had chronic heart failure in New York Heart Association functional class II-IV and with a left ventricular ejection fraction of 40% or less, the standard ejection fraction criterion for defining HFrEF. Half the enrolled patients had diabetes, and analysis showed no heterogeneity in the primary outcome response based on diabetes status at enrollment.
Empagliflozin joins dapagliflozin for treating HFrEF
Dapagliflozin (Farxiga) was the first agent from the SGLT2 inhibitor class to receive an FDA indication, in 2020, for treating patients with HFrEF regardless of their diabetes status, a decision based on results from the DAPA-HF trial. Results from DAPA-HF showed that treatment with dapagliflozin in patients with HFrEF for a median of 18 months led to a 26% relative reduction in the incidence of cardiovascular death or worsening heart failure and a 4.9% absolute reduction, compared with placebo when added to standard treatment. DAPA-HF enrolled patients using similar criteria to EMPEROR-Reduced, and 42% of enrolled patients had diabetes with no heterogeneity in the primary outcome related to baseline diabetes status.
Subsequent to the report of results from the EMPEROR-Reduced trial nearly a year ago, heart failure experts declared that treatment with an agent from the SGLT2 inhibitor class had become a “new pillar of foundational therapy for HFrEF,” and they urged rapid initiation of an SGLT2 inhibitor (along with other appropriate medications) at the time of initial diagnosis of HFrEF.
The U.S. Food and Drug Administration approved empagliflozin (Jardiance) as a treatment for adults with heart failure with reduced ejection fraction (HFrEF) regardless of whether patients have diabetes on Aug. 18, making it the second agent from the sodium-glucose transporter 2 inhibitor class to received this indication.
Empagliflozin first received FDA marketing approval in 2014 for improving glycemic control in patients with type 2 diabetes, and in 2016 the agency added a second indication of reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease. The newly granted indication for patients with HFrEF without regard to glycemic status was for reducing the risk for cardiovascular death and hospitalization for heart failure, according to a statement from Boehringer Ingelheim and Lilly, the two companies that together market empagliflozin.
The statement also said that the approval allowed for empagliflozin treatment in patients with HFrEF and an estimated glomerular filtration rate (eGFR) as low as 20 mL/min per 1.73 m2, in contrast to its indication for improving glycemic control in patients with type 2 diabetes that limits use to patients with an eGFR of at least 30 mL per 1.73 m2.
EMPEROR-Reduced results drive approval
The FDA based its decision on results from the EMPEROR-Reduced study, first reported in August 2020, that showed treatment of patients with HFrEF with empagliflozin on top of standard therapy for a median of 16 months cut the incidence of cardiovascular death or hospitalization for worsening heart failure by 25% relative to placebo, and by an absolute 5.3%, compared with placebo-treated patients.
Patients enrolled in EMPEROR-Reduced had chronic heart failure in New York Heart Association functional class II-IV and with a left ventricular ejection fraction of 40% or less, the standard ejection fraction criterion for defining HFrEF. Half the enrolled patients had diabetes, and analysis showed no heterogeneity in the primary outcome response based on diabetes status at enrollment.
Empagliflozin joins dapagliflozin for treating HFrEF
Dapagliflozin (Farxiga) was the first agent from the SGLT2 inhibitor class to receive an FDA indication, in 2020, for treating patients with HFrEF regardless of their diabetes status, a decision based on results from the DAPA-HF trial. Results from DAPA-HF showed that treatment with dapagliflozin in patients with HFrEF for a median of 18 months led to a 26% relative reduction in the incidence of cardiovascular death or worsening heart failure and a 4.9% absolute reduction, compared with placebo when added to standard treatment. DAPA-HF enrolled patients using similar criteria to EMPEROR-Reduced, and 42% of enrolled patients had diabetes with no heterogeneity in the primary outcome related to baseline diabetes status.
Subsequent to the report of results from the EMPEROR-Reduced trial nearly a year ago, heart failure experts declared that treatment with an agent from the SGLT2 inhibitor class had become a “new pillar of foundational therapy for HFrEF,” and they urged rapid initiation of an SGLT2 inhibitor (along with other appropriate medications) at the time of initial diagnosis of HFrEF.
The U.S. Food and Drug Administration approved empagliflozin (Jardiance) as a treatment for adults with heart failure with reduced ejection fraction (HFrEF) regardless of whether patients have diabetes on Aug. 18, making it the second agent from the sodium-glucose transporter 2 inhibitor class to received this indication.
Empagliflozin first received FDA marketing approval in 2014 for improving glycemic control in patients with type 2 diabetes, and in 2016 the agency added a second indication of reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease. The newly granted indication for patients with HFrEF without regard to glycemic status was for reducing the risk for cardiovascular death and hospitalization for heart failure, according to a statement from Boehringer Ingelheim and Lilly, the two companies that together market empagliflozin.
The statement also said that the approval allowed for empagliflozin treatment in patients with HFrEF and an estimated glomerular filtration rate (eGFR) as low as 20 mL/min per 1.73 m2, in contrast to its indication for improving glycemic control in patients with type 2 diabetes that limits use to patients with an eGFR of at least 30 mL per 1.73 m2.
EMPEROR-Reduced results drive approval
The FDA based its decision on results from the EMPEROR-Reduced study, first reported in August 2020, that showed treatment of patients with HFrEF with empagliflozin on top of standard therapy for a median of 16 months cut the incidence of cardiovascular death or hospitalization for worsening heart failure by 25% relative to placebo, and by an absolute 5.3%, compared with placebo-treated patients.
Patients enrolled in EMPEROR-Reduced had chronic heart failure in New York Heart Association functional class II-IV and with a left ventricular ejection fraction of 40% or less, the standard ejection fraction criterion for defining HFrEF. Half the enrolled patients had diabetes, and analysis showed no heterogeneity in the primary outcome response based on diabetes status at enrollment.
Empagliflozin joins dapagliflozin for treating HFrEF
Dapagliflozin (Farxiga) was the first agent from the SGLT2 inhibitor class to receive an FDA indication, in 2020, for treating patients with HFrEF regardless of their diabetes status, a decision based on results from the DAPA-HF trial. Results from DAPA-HF showed that treatment with dapagliflozin in patients with HFrEF for a median of 18 months led to a 26% relative reduction in the incidence of cardiovascular death or worsening heart failure and a 4.9% absolute reduction, compared with placebo when added to standard treatment. DAPA-HF enrolled patients using similar criteria to EMPEROR-Reduced, and 42% of enrolled patients had diabetes with no heterogeneity in the primary outcome related to baseline diabetes status.
Subsequent to the report of results from the EMPEROR-Reduced trial nearly a year ago, heart failure experts declared that treatment with an agent from the SGLT2 inhibitor class had become a “new pillar of foundational therapy for HFrEF,” and they urged rapid initiation of an SGLT2 inhibitor (along with other appropriate medications) at the time of initial diagnosis of HFrEF.
Pandemic derails small success in lowering diabetes-related amputations
Rates of minor diabetes-related lower extremity amputations (LEAs) in hospitalized patients increased between 2009 and 2017 in all racial and ethnic groups, in both rural and urban areas, and in all geographic regions across the United States, a new retrospective, observational study indicates.
In contrast, major lower extremity amputation rates held steady during the study period with a few exceptions.
There was also a decline in major-to-minor amputation ratios, especially among Native Americans – a sign that diabetes was being better managed and foot ulcers were being caught earlier, preventing the need for a major amputation above the foot or below or above the knee.
Minor LEAs include the loss of a toe, toes, or a foot.
“While I know an amputation is devastating either way, having a minor amputation is better than having a major amputation, and trends [at least to 2017] show that comprehensive foot examinations are paying off,” lead author Marvellous Akinlotan, PhD, MPH, a research associate at the Southwest Rural Health Research Center in Bryan, Texas, said in an interview.
Asked to comment, Marcia Ory, PhD, MPH, director of the Center for Population Health & Aging, Texas A&M School of Public Health, College Station, who was not involved in the study, said: “It points to some successes, but it also points to the need for continued education and preventive care to reduce all types of amputations.”
The study was published online in Diabetes Care.
Amputations increased during COVID-19
However, the study was conducted prior to the COVID-19 pandemic, and amputation rates appear to have significantly worsened during the past 18 months.
In a summary of recent evidence collated by the Amputee Coalition, the authors point out that not only does COVID-19 itself put patients at higher risk for limb loss because severe infection increases the risk of blood clots, but patients with diabetes appear to have been far more likely to undergo any level of amputation during the pandemic than before it began.
In a study of patients with diabetes attending a foot and ankle surgery service in Ohio, the risk of having any level of amputation was 10.8 times higher during compared with before the pandemic. And of patients undergoing any amputation, the odds for receiving a major amputation was 3.1 times higher than before the pandemic.
Telehealth and web-based options for diabetes care and education could help improve health outcomes, particularly during lockdowns.
“Having a diabetes-related amputation is life-changing – it brings disability and functional limitations to the individual – and within the health care system, it reflects the failure of secondary prevention efforts, which ideally should slow the progression of diabetic complications,” noted Dr. Akinlotan.
Race and geography affect risk of amputation
In their study, Dr. Akinlotan and colleagues used data from the National Inpatient Sample to identify trends in LEAs among patients primarily hospitalized for diabetes in the United States between 2009 and 2017.
“The primary outcome variable was documentation of either minor or major LEA during a diabetes-related admission,” they explain.
Minor LEAs increased significantly across all ethnic groups.
Although major amputation rates remained steady, “we did find that some groups remained at risk for having a major amputation,” Dr. Akinlotan noted.
White populations, people in the Midwest, and rural areas saw notable increases in major LEAs, as did “... Blacks, Hispanics, [and] those living in the South,” she said.
Patients need to be encouraged to monitor and control their blood glucose, to offset modifiable risk factors, and to seek regular medical attention to prevent an insidious diabetic complication from developing further, she said.
“It’s important for patients to know that continuing care is necessary,” Dr. Akinlotan stressed. “Diabetes is chronic and complex, but it can be managed, so that’s the good news.”
Dr. Ory agrees: “Effective management will require an all-in approach, with doctors and patients working together.
“Given the limited time in doctor-patient encounters, physicians can benefit patients by referring them to evidence-based, self-management education programs, which are proliferating around in the county,” she added.
The authors and Dr. Ory have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rates of minor diabetes-related lower extremity amputations (LEAs) in hospitalized patients increased between 2009 and 2017 in all racial and ethnic groups, in both rural and urban areas, and in all geographic regions across the United States, a new retrospective, observational study indicates.
In contrast, major lower extremity amputation rates held steady during the study period with a few exceptions.
There was also a decline in major-to-minor amputation ratios, especially among Native Americans – a sign that diabetes was being better managed and foot ulcers were being caught earlier, preventing the need for a major amputation above the foot or below or above the knee.
Minor LEAs include the loss of a toe, toes, or a foot.
“While I know an amputation is devastating either way, having a minor amputation is better than having a major amputation, and trends [at least to 2017] show that comprehensive foot examinations are paying off,” lead author Marvellous Akinlotan, PhD, MPH, a research associate at the Southwest Rural Health Research Center in Bryan, Texas, said in an interview.
Asked to comment, Marcia Ory, PhD, MPH, director of the Center for Population Health & Aging, Texas A&M School of Public Health, College Station, who was not involved in the study, said: “It points to some successes, but it also points to the need for continued education and preventive care to reduce all types of amputations.”
The study was published online in Diabetes Care.
Amputations increased during COVID-19
However, the study was conducted prior to the COVID-19 pandemic, and amputation rates appear to have significantly worsened during the past 18 months.
In a summary of recent evidence collated by the Amputee Coalition, the authors point out that not only does COVID-19 itself put patients at higher risk for limb loss because severe infection increases the risk of blood clots, but patients with diabetes appear to have been far more likely to undergo any level of amputation during the pandemic than before it began.
In a study of patients with diabetes attending a foot and ankle surgery service in Ohio, the risk of having any level of amputation was 10.8 times higher during compared with before the pandemic. And of patients undergoing any amputation, the odds for receiving a major amputation was 3.1 times higher than before the pandemic.
Telehealth and web-based options for diabetes care and education could help improve health outcomes, particularly during lockdowns.
“Having a diabetes-related amputation is life-changing – it brings disability and functional limitations to the individual – and within the health care system, it reflects the failure of secondary prevention efforts, which ideally should slow the progression of diabetic complications,” noted Dr. Akinlotan.
Race and geography affect risk of amputation
In their study, Dr. Akinlotan and colleagues used data from the National Inpatient Sample to identify trends in LEAs among patients primarily hospitalized for diabetes in the United States between 2009 and 2017.
“The primary outcome variable was documentation of either minor or major LEA during a diabetes-related admission,” they explain.
Minor LEAs increased significantly across all ethnic groups.
Although major amputation rates remained steady, “we did find that some groups remained at risk for having a major amputation,” Dr. Akinlotan noted.
White populations, people in the Midwest, and rural areas saw notable increases in major LEAs, as did “... Blacks, Hispanics, [and] those living in the South,” she said.
Patients need to be encouraged to monitor and control their blood glucose, to offset modifiable risk factors, and to seek regular medical attention to prevent an insidious diabetic complication from developing further, she said.
“It’s important for patients to know that continuing care is necessary,” Dr. Akinlotan stressed. “Diabetes is chronic and complex, but it can be managed, so that’s the good news.”
Dr. Ory agrees: “Effective management will require an all-in approach, with doctors and patients working together.
“Given the limited time in doctor-patient encounters, physicians can benefit patients by referring them to evidence-based, self-management education programs, which are proliferating around in the county,” she added.
The authors and Dr. Ory have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rates of minor diabetes-related lower extremity amputations (LEAs) in hospitalized patients increased between 2009 and 2017 in all racial and ethnic groups, in both rural and urban areas, and in all geographic regions across the United States, a new retrospective, observational study indicates.
In contrast, major lower extremity amputation rates held steady during the study period with a few exceptions.
There was also a decline in major-to-minor amputation ratios, especially among Native Americans – a sign that diabetes was being better managed and foot ulcers were being caught earlier, preventing the need for a major amputation above the foot or below or above the knee.
Minor LEAs include the loss of a toe, toes, or a foot.
“While I know an amputation is devastating either way, having a minor amputation is better than having a major amputation, and trends [at least to 2017] show that comprehensive foot examinations are paying off,” lead author Marvellous Akinlotan, PhD, MPH, a research associate at the Southwest Rural Health Research Center in Bryan, Texas, said in an interview.
Asked to comment, Marcia Ory, PhD, MPH, director of the Center for Population Health & Aging, Texas A&M School of Public Health, College Station, who was not involved in the study, said: “It points to some successes, but it also points to the need for continued education and preventive care to reduce all types of amputations.”
The study was published online in Diabetes Care.
Amputations increased during COVID-19
However, the study was conducted prior to the COVID-19 pandemic, and amputation rates appear to have significantly worsened during the past 18 months.
In a summary of recent evidence collated by the Amputee Coalition, the authors point out that not only does COVID-19 itself put patients at higher risk for limb loss because severe infection increases the risk of blood clots, but patients with diabetes appear to have been far more likely to undergo any level of amputation during the pandemic than before it began.
In a study of patients with diabetes attending a foot and ankle surgery service in Ohio, the risk of having any level of amputation was 10.8 times higher during compared with before the pandemic. And of patients undergoing any amputation, the odds for receiving a major amputation was 3.1 times higher than before the pandemic.
Telehealth and web-based options for diabetes care and education could help improve health outcomes, particularly during lockdowns.
“Having a diabetes-related amputation is life-changing – it brings disability and functional limitations to the individual – and within the health care system, it reflects the failure of secondary prevention efforts, which ideally should slow the progression of diabetic complications,” noted Dr. Akinlotan.
Race and geography affect risk of amputation
In their study, Dr. Akinlotan and colleagues used data from the National Inpatient Sample to identify trends in LEAs among patients primarily hospitalized for diabetes in the United States between 2009 and 2017.
“The primary outcome variable was documentation of either minor or major LEA during a diabetes-related admission,” they explain.
Minor LEAs increased significantly across all ethnic groups.
Although major amputation rates remained steady, “we did find that some groups remained at risk for having a major amputation,” Dr. Akinlotan noted.
White populations, people in the Midwest, and rural areas saw notable increases in major LEAs, as did “... Blacks, Hispanics, [and] those living in the South,” she said.
Patients need to be encouraged to monitor and control their blood glucose, to offset modifiable risk factors, and to seek regular medical attention to prevent an insidious diabetic complication from developing further, she said.
“It’s important for patients to know that continuing care is necessary,” Dr. Akinlotan stressed. “Diabetes is chronic and complex, but it can be managed, so that’s the good news.”
Dr. Ory agrees: “Effective management will require an all-in approach, with doctors and patients working together.
“Given the limited time in doctor-patient encounters, physicians can benefit patients by referring them to evidence-based, self-management education programs, which are proliferating around in the county,” she added.
The authors and Dr. Ory have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.