Lipid Disorders

Further analyses from the cardiovascular outcome trial of the sodium-glucose transporter 2 inhibitor ertugliflozin in patients with type 2 diabetes helped better define positive effects the drug had on preserving renal function, and also gave a tantalizing hint that this drug, and hence possibly the entire SGLT2 inhibitor drug class, may benefit patients with heart failure with reduced ejection fraction.

But the underlying problem for ertugliflozin (Steglatro) – first seen when results from the VERTIS CV trial initially came out in June 2020 at the annual meeting of the American Diabetes Association – was that, while the trial met its primary endpoint of proving noninferiority to placebo for the combined endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke, treatment with ertugliflozin showed no suggestion of benefit, compared with placebo for reducing this endpoint, producing a nonsignificant 3% relative cut in the combined rate of these adverse events, compared with placebo treatment.
 

‘Somewhat disappointing’ trial performance

Overall, results from VERTIS CV with ertugliflozin were “somewhat disappointing,” commented Melanie J. Davies, MD, who was not involved with the study and chaired a session at the virtual annual meeting of the European Association for the Study of Diabetes that reviewed the main results, put them into perspective, and added a few new exploratory analyses.

Although the results from 8,246-patient VERTIS CV (Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial) put ertugliflozin in the same league as other drugs from its class for safety, “we do not see the significant benefits observed in many of the previous cardiovascular outcomes trials” for other drugs in the SGLT2 inhibitor class, specifically canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), Dr. Davies said in an interview. The upshot, for at least the time being, is that ertugliflozin “is unlikely to receive a label for any new indications,” she predicted. In contrast, the other drugs in the class have, for example, received a U.S. labeled indication to reduce cardiovascular death (empagliflozin) or major cardiovascular disease events (canagliflozin) in adults with type 2 diabetes (T2D) and cardiovascular disease, or to reduce heart failure hospitalizations (dapagliflozin).

The main results from VERTIS CV, posted online in the New England Journal of Medicine after the EASD session, showed a single significant outcome difference between treatment with ertugliflozin and placebo over a median of 3.0 years of follow-up from among 10 reported secondary outcomes: a 30% relative reduction (a 1.1% absolute reduction) in the rate of hospitalization for heart failure, the sole criterion in the report by which ertugliflozin matched the benefits of the other SGLT2 inhibitors.

But the prespecified design of VERTIS CV called for a hierarchical sequence of secondary analyses. The statistically significant noninferiority of the primary endpoint allowed calculation of the initial secondary endpoint, a reduction in the combined rate of cardiovascular death or hospitalization for heart failure. Ertugliflozin treatment cut this outcome by a relative 12%, compared with placebo, a difference that was not significant.

This neutral finding brought to a stop further statistical testing of any of the other secondary endpoints, including impact on hospitalization for heart failure by itself. It also guaranteed that no beneficial effect inferred from the trial’s data would qualify for statistical validity, making it unlikely that ertugliflozin would gain any new label indications from these results. The drug carries a U.S. label that is limited to providing glycemic control.

Choosing among the SGLT2 inhibitors

“What we can say for sure is that there is a glycemic benefit and a heart failure hospitalization benefit” across all four of the SGLT2 inhibitors. “Beyond that, the best we can say today [about using these drugs in practice] is to follow regulatory indications and guidelines recommendations,” commented Javed Butler, MD, a cardiologist and professor and chair of medicine at the University of Mississippi Medical Center, Jackson.

“These results are going to lead to some serious discussions among the research, clinical, and regulatory communities about class effects versus drug effects, and specific trial data versus the totality of evidence,” he said in an interview.

“I think it will influence prescribing ertugliflozin, particularly in patients with established cardiovascular disease, or when the goal is to improve heart failure outcomes of reduce chronic kidney disease,” added Dr. Davies, a professor of diabetes medicine at the University of Leicester (England). “We already have positive benefits [proven for these outcomes] using other agents in the class.”

Perhaps one feature potentially in ertugliflozin’s favor is its price, and whatever impact that might have for payers or patients with inadequate coverage for their drug costs. U.S. websites show a typical retail price for ertugliflozin that is roughly 40% below the three other agents in the class, a difference that can add up to an annual cost savings of about $2,500.

A major consideration for clinicians deciding which SGLT2 inhibitor to prescribe should be “what can the patient afford,” noted Darren K. McGuire, MD, a coinvestigator for VERTIS CV, during discussion of the trial at the EASD virtual meeting.
 

New analyses show more renal-effect consistency

One surprise in the initial VERTIS CV report was in the study’s key renal outcome, a composite of renal death, need for dialysis, or a doubling of the serum creatinine level, which reflects a cut of at least a 50% in estimated glomerular filtration rate (eGFR). This composite outcome trended toward a significant benefit but fell short, producing a nominal 19% relative reduction. This combined endpoint probably “set the bar too high,” said David Z.I. Cherney, MD, a nephrologist who led the renal assessments run in the trial. He presented several exploratory analyses during the virtual EASD session that provided reassuring evidence that ertugliflozin was not an outlier among the SGLT2 inhibitors when it came to kidney benefits.

Perhaps the most compelling analysis he reported was a slight tweak to the main renal composite endpoint that substituted prevention of a 40% or greater reduction in eGFR for prevention of a 50% or greater reduction. By this somewhat lower bar for efficacy, treatment with ertugliflozin in VERTIS CV linked with a 34% relative risk reduction, compared with placebo (a roughly 1% absolute reduction) that was statistically significant, and importantly came out very close to the effect for this revised endpoint that had been seen for the other three SGLT2 inhibitor drugs.

Focusing on prevention of a 40% or greater drop in eGFR “gives a much more robust measure of renal protection,” Dr. Cherney, a clinician and researcher at the University of Toronto, said in an interview. “The key message is that renal protection is much more uniform” with the rest of the drugs in the class when looked at this way or by some of the other alternative parameters he reported. But the new renal analyses do not address disparities seen among the drugs in the class for several cardiovascular disease effects.

“The overall impression from VERTIS CV is that there was less cardiovascular disease benefit,” except for prevention of heart failure hospitalization, he said.

A teaser for HFpEF

One additional notable new finding discussed during the EASD session stemmed from the investigators ability to mine the medical records of enrolled patients for information about their heart failure history and left ventricular ejection fractions, a data set that was “unique,” compared with the other cardiovascular outcome trials for the drugs in the class, noted Francesco Cosentino, MD, another VERTIS CV coinvestigator and professor of cardiology at the Karolinska Institute in Stockholm.

Roughly a quarter of the enrolled patients had a history of heart failure, and about half of these patients had heart failure with preserved ejection fraction, about 1,000 total patients. In this subgroup treatment with ertugliflozin linked with a 30% relative reduction in hospitalization for heart failure, compared with placebo, a roughly 0.5% absolute reduction. The numbers were small and underpowered for producing convincing evidence, but it provided an intriguing hint of benefit for an unmet need that is currently undergoing further testing in studies designed to specifically explore benefit in this type of heart failure patient, said Dr. Cosentino.

VERTIS CV was sponsored by Merck and Pfizer, the companies that market ertugliflozin. Dr. Davies has been a speaker on behalf of Merck and has had relationships with several other companies. Dr. Butler is a consultant to Merck and several other companies. Dr. McGuire has received honoraria from Merck, nonfinancial support from Pfizer, and has had relationships with several other companies. Dr. Cherney has received honoraria from Merck, nonfinancial research support from Pfizer, and has also had relationships with several other companies. Dr. Cosentino has received fees from Merck and Pfizer, and also from Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb, and Novo Nordisk

[email protected]

Further analyses from the cardiovascular outcome trial of the sodium-glucose transporter 2 inhibitor ertugliflozin in patients with type 2 diabetes helped better define positive effects the drug had on preserving renal function, and also gave a tantalizing hint that this drug, and hence possibly the entire SGLT2 inhibitor drug class, may benefit patients with heart failure with reduced ejection fraction.

But the underlying problem for ertugliflozin (Steglatro) – first seen when results from the VERTIS CV trial initially came out in June 2020 at the annual meeting of the American Diabetes Association – was that, while the trial met its primary endpoint of proving noninferiority to placebo for the combined endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke, treatment with ertugliflozin showed no suggestion of benefit, compared with placebo for reducing this endpoint, producing a nonsignificant 3% relative cut in the combined rate of these adverse events, compared with placebo treatment.
 

‘Somewhat disappointing’ trial performance

Overall, results from VERTIS CV with ertugliflozin were “somewhat disappointing,” commented Melanie J. Davies, MD, who was not involved with the study and chaired a session at the virtual annual meeting of the European Association for the Study of Diabetes that reviewed the main results, put them into perspective, and added a few new exploratory analyses.

Although the results from 8,246-patient VERTIS CV (Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial) put ertugliflozin in the same league as other drugs from its class for safety, “we do not see the significant benefits observed in many of the previous cardiovascular outcomes trials” for other drugs in the SGLT2 inhibitor class, specifically canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), Dr. Davies said in an interview. The upshot, for at least the time being, is that ertugliflozin “is unlikely to receive a label for any new indications,” she predicted. In contrast, the other drugs in the class have, for example, received a U.S. labeled indication to reduce cardiovascular death (empagliflozin) or major cardiovascular disease events (canagliflozin) in adults with type 2 diabetes (T2D) and cardiovascular disease, or to reduce heart failure hospitalizations (dapagliflozin).

The main results from VERTIS CV, posted online in the New England Journal of Medicine after the EASD session, showed a single significant outcome difference between treatment with ertugliflozin and placebo over a median of 3.0 years of follow-up from among 10 reported secondary outcomes: a 30% relative reduction (a 1.1% absolute reduction) in the rate of hospitalization for heart failure, the sole criterion in the report by which ertugliflozin matched the benefits of the other SGLT2 inhibitors.

But the prespecified design of VERTIS CV called for a hierarchical sequence of secondary analyses. The statistically significant noninferiority of the primary endpoint allowed calculation of the initial secondary endpoint, a reduction in the combined rate of cardiovascular death or hospitalization for heart failure. Ertugliflozin treatment cut this outcome by a relative 12%, compared with placebo, a difference that was not significant.

This neutral finding brought to a stop further statistical testing of any of the other secondary endpoints, including impact on hospitalization for heart failure by itself. It also guaranteed that no beneficial effect inferred from the trial’s data would qualify for statistical validity, making it unlikely that ertugliflozin would gain any new label indications from these results. The drug carries a U.S. label that is limited to providing glycemic control.

Choosing among the SGLT2 inhibitors

“What we can say for sure is that there is a glycemic benefit and a heart failure hospitalization benefit” across all four of the SGLT2 inhibitors. “Beyond that, the best we can say today [about using these drugs in practice] is to follow regulatory indications and guidelines recommendations,” commented Javed Butler, MD, a cardiologist and professor and chair of medicine at the University of Mississippi Medical Center, Jackson.

“These results are going to lead to some serious discussions among the research, clinical, and regulatory communities about class effects versus drug effects, and specific trial data versus the totality of evidence,” he said in an interview.

“I think it will influence prescribing ertugliflozin, particularly in patients with established cardiovascular disease, or when the goal is to improve heart failure outcomes of reduce chronic kidney disease,” added Dr. Davies, a professor of diabetes medicine at the University of Leicester (England). “We already have positive benefits [proven for these outcomes] using other agents in the class.”

Perhaps one feature potentially in ertugliflozin’s favor is its price, and whatever impact that might have for payers or patients with inadequate coverage for their drug costs. U.S. websites show a typical retail price for ertugliflozin that is roughly 40% below the three other agents in the class, a difference that can add up to an annual cost savings of about $2,500.

A major consideration for clinicians deciding which SGLT2 inhibitor to prescribe should be “what can the patient afford,” noted Darren K. McGuire, MD, a coinvestigator for VERTIS CV, during discussion of the trial at the EASD virtual meeting.
 

New analyses show more renal-effect consistency

One surprise in the initial VERTIS CV report was in the study’s key renal outcome, a composite of renal death, need for dialysis, or a doubling of the serum creatinine level, which reflects a cut of at least a 50% in estimated glomerular filtration rate (eGFR). This composite outcome trended toward a significant benefit but fell short, producing a nominal 19% relative reduction. This combined endpoint probably “set the bar too high,” said David Z.I. Cherney, MD, a nephrologist who led the renal assessments run in the trial. He presented several exploratory analyses during the virtual EASD session that provided reassuring evidence that ertugliflozin was not an outlier among the SGLT2 inhibitors when it came to kidney benefits.

Perhaps the most compelling analysis he reported was a slight tweak to the main renal composite endpoint that substituted prevention of a 40% or greater reduction in eGFR for prevention of a 50% or greater reduction. By this somewhat lower bar for efficacy, treatment with ertugliflozin in VERTIS CV linked with a 34% relative risk reduction, compared with placebo (a roughly 1% absolute reduction) that was statistically significant, and importantly came out very close to the effect for this revised endpoint that had been seen for the other three SGLT2 inhibitor drugs.

Focusing on prevention of a 40% or greater drop in eGFR “gives a much more robust measure of renal protection,” Dr. Cherney, a clinician and researcher at the University of Toronto, said in an interview. “The key message is that renal protection is much more uniform” with the rest of the drugs in the class when looked at this way or by some of the other alternative parameters he reported. But the new renal analyses do not address disparities seen among the drugs in the class for several cardiovascular disease effects.

“The overall impression from VERTIS CV is that there was less cardiovascular disease benefit,” except for prevention of heart failure hospitalization, he said.

A teaser for HFpEF

One additional notable new finding discussed during the EASD session stemmed from the investigators ability to mine the medical records of enrolled patients for information about their heart failure history and left ventricular ejection fractions, a data set that was “unique,” compared with the other cardiovascular outcome trials for the drugs in the class, noted Francesco Cosentino, MD, another VERTIS CV coinvestigator and professor of cardiology at the Karolinska Institute in Stockholm.

Roughly a quarter of the enrolled patients had a history of heart failure, and about half of these patients had heart failure with preserved ejection fraction, about 1,000 total patients. In this subgroup treatment with ertugliflozin linked with a 30% relative reduction in hospitalization for heart failure, compared with placebo, a roughly 0.5% absolute reduction. The numbers were small and underpowered for producing convincing evidence, but it provided an intriguing hint of benefit for an unmet need that is currently undergoing further testing in studies designed to specifically explore benefit in this type of heart failure patient, said Dr. Cosentino.

VERTIS CV was sponsored by Merck and Pfizer, the companies that market ertugliflozin. Dr. Davies has been a speaker on behalf of Merck and has had relationships with several other companies. Dr. Butler is a consultant to Merck and several other companies. Dr. McGuire has received honoraria from Merck, nonfinancial support from Pfizer, and has had relationships with several other companies. Dr. Cherney has received honoraria from Merck, nonfinancial research support from Pfizer, and has also had relationships with several other companies. Dr. Cosentino has received fees from Merck and Pfizer, and also from Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb, and Novo Nordisk

[email protected]

Further analyses from the cardiovascular outcome trial of the sodium-glucose transporter 2 inhibitor ertugliflozin in patients with type 2 diabetes helped better define positive effects the drug had on preserving renal function, and also gave a tantalizing hint that this drug, and hence possibly the entire SGLT2 inhibitor drug class, may benefit patients with heart failure with reduced ejection fraction.

But the underlying problem for ertugliflozin (Steglatro) – first seen when results from the VERTIS CV trial initially came out in June 2020 at the annual meeting of the American Diabetes Association – was that, while the trial met its primary endpoint of proving noninferiority to placebo for the combined endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke, treatment with ertugliflozin showed no suggestion of benefit, compared with placebo for reducing this endpoint, producing a nonsignificant 3% relative cut in the combined rate of these adverse events, compared with placebo treatment.
 

‘Somewhat disappointing’ trial performance

Overall, results from VERTIS CV with ertugliflozin were “somewhat disappointing,” commented Melanie J. Davies, MD, who was not involved with the study and chaired a session at the virtual annual meeting of the European Association for the Study of Diabetes that reviewed the main results, put them into perspective, and added a few new exploratory analyses.

Although the results from 8,246-patient VERTIS CV (Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial) put ertugliflozin in the same league as other drugs from its class for safety, “we do not see the significant benefits observed in many of the previous cardiovascular outcomes trials” for other drugs in the SGLT2 inhibitor class, specifically canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), Dr. Davies said in an interview. The upshot, for at least the time being, is that ertugliflozin “is unlikely to receive a label for any new indications,” she predicted. In contrast, the other drugs in the class have, for example, received a U.S. labeled indication to reduce cardiovascular death (empagliflozin) or major cardiovascular disease events (canagliflozin) in adults with type 2 diabetes (T2D) and cardiovascular disease, or to reduce heart failure hospitalizations (dapagliflozin).

The main results from VERTIS CV, posted online in the New England Journal of Medicine after the EASD session, showed a single significant outcome difference between treatment with ertugliflozin and placebo over a median of 3.0 years of follow-up from among 10 reported secondary outcomes: a 30% relative reduction (a 1.1% absolute reduction) in the rate of hospitalization for heart failure, the sole criterion in the report by which ertugliflozin matched the benefits of the other SGLT2 inhibitors.

But the prespecified design of VERTIS CV called for a hierarchical sequence of secondary analyses. The statistically significant noninferiority of the primary endpoint allowed calculation of the initial secondary endpoint, a reduction in the combined rate of cardiovascular death or hospitalization for heart failure. Ertugliflozin treatment cut this outcome by a relative 12%, compared with placebo, a difference that was not significant.

This neutral finding brought to a stop further statistical testing of any of the other secondary endpoints, including impact on hospitalization for heart failure by itself. It also guaranteed that no beneficial effect inferred from the trial’s data would qualify for statistical validity, making it unlikely that ertugliflozin would gain any new label indications from these results. The drug carries a U.S. label that is limited to providing glycemic control.

Choosing among the SGLT2 inhibitors

“What we can say for sure is that there is a glycemic benefit and a heart failure hospitalization benefit” across all four of the SGLT2 inhibitors. “Beyond that, the best we can say today [about using these drugs in practice] is to follow regulatory indications and guidelines recommendations,” commented Javed Butler, MD, a cardiologist and professor and chair of medicine at the University of Mississippi Medical Center, Jackson.

“These results are going to lead to some serious discussions among the research, clinical, and regulatory communities about class effects versus drug effects, and specific trial data versus the totality of evidence,” he said in an interview.

“I think it will influence prescribing ertugliflozin, particularly in patients with established cardiovascular disease, or when the goal is to improve heart failure outcomes of reduce chronic kidney disease,” added Dr. Davies, a professor of diabetes medicine at the University of Leicester (England). “We already have positive benefits [proven for these outcomes] using other agents in the class.”

Perhaps one feature potentially in ertugliflozin’s favor is its price, and whatever impact that might have for payers or patients with inadequate coverage for their drug costs. U.S. websites show a typical retail price for ertugliflozin that is roughly 40% below the three other agents in the class, a difference that can add up to an annual cost savings of about $2,500.

A major consideration for clinicians deciding which SGLT2 inhibitor to prescribe should be “what can the patient afford,” noted Darren K. McGuire, MD, a coinvestigator for VERTIS CV, during discussion of the trial at the EASD virtual meeting.
 

New analyses show more renal-effect consistency

One surprise in the initial VERTIS CV report was in the study’s key renal outcome, a composite of renal death, need for dialysis, or a doubling of the serum creatinine level, which reflects a cut of at least a 50% in estimated glomerular filtration rate (eGFR). This composite outcome trended toward a significant benefit but fell short, producing a nominal 19% relative reduction. This combined endpoint probably “set the bar too high,” said David Z.I. Cherney, MD, a nephrologist who led the renal assessments run in the trial. He presented several exploratory analyses during the virtual EASD session that provided reassuring evidence that ertugliflozin was not an outlier among the SGLT2 inhibitors when it came to kidney benefits.

Perhaps the most compelling analysis he reported was a slight tweak to the main renal composite endpoint that substituted prevention of a 40% or greater reduction in eGFR for prevention of a 50% or greater reduction. By this somewhat lower bar for efficacy, treatment with ertugliflozin in VERTIS CV linked with a 34% relative risk reduction, compared with placebo (a roughly 1% absolute reduction) that was statistically significant, and importantly came out very close to the effect for this revised endpoint that had been seen for the other three SGLT2 inhibitor drugs.

Focusing on prevention of a 40% or greater drop in eGFR “gives a much more robust measure of renal protection,” Dr. Cherney, a clinician and researcher at the University of Toronto, said in an interview. “The key message is that renal protection is much more uniform” with the rest of the drugs in the class when looked at this way or by some of the other alternative parameters he reported. But the new renal analyses do not address disparities seen among the drugs in the class for several cardiovascular disease effects.

“The overall impression from VERTIS CV is that there was less cardiovascular disease benefit,” except for prevention of heart failure hospitalization, he said.

A teaser for HFpEF

One additional notable new finding discussed during the EASD session stemmed from the investigators ability to mine the medical records of enrolled patients for information about their heart failure history and left ventricular ejection fractions, a data set that was “unique,” compared with the other cardiovascular outcome trials for the drugs in the class, noted Francesco Cosentino, MD, another VERTIS CV coinvestigator and professor of cardiology at the Karolinska Institute in Stockholm.

Roughly a quarter of the enrolled patients had a history of heart failure, and about half of these patients had heart failure with preserved ejection fraction, about 1,000 total patients. In this subgroup treatment with ertugliflozin linked with a 30% relative reduction in hospitalization for heart failure, compared with placebo, a roughly 0.5% absolute reduction. The numbers were small and underpowered for producing convincing evidence, but it provided an intriguing hint of benefit for an unmet need that is currently undergoing further testing in studies designed to specifically explore benefit in this type of heart failure patient, said Dr. Cosentino.

VERTIS CV was sponsored by Merck and Pfizer, the companies that market ertugliflozin. Dr. Davies has been a speaker on behalf of Merck and has had relationships with several other companies. Dr. Butler is a consultant to Merck and several other companies. Dr. McGuire has received honoraria from Merck, nonfinancial support from Pfizer, and has had relationships with several other companies. Dr. Cherney has received honoraria from Merck, nonfinancial research support from Pfizer, and has also had relationships with several other companies. Dr. Cosentino has received fees from Merck and Pfizer, and also from Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb, and Novo Nordisk

[email protected]

Not only the prevalence, but the impact of nonalcoholic fatty liver disease (NAFLD) is increasing in much of the world, Arun J. Sanyal, MD, said in a virtual presentation at the meeting jointly provided by Rutgers and Global Academy for Medical Education. “It is currently estimated that the number of people living with cirrhosis or with decompensated cirrhosis will increase two- to threefold from 2015 to 2030,” which underlines the public health impact and the need for improved treatment paradigms, he emphasized.

“The thing to remember about NAFLD is that it does not exist in a vacuum,” Dr. Sanyal said. NAFLD is a multisystem disorder. Most patients have concomitant cardiovascular disease, but others may have type 2 diabetes, hypertension, and dyslipidemia, all of which are now accepted as risk factors for nonalcoholic steatohepatitis (NASH), he said.

“What ties these conditions together is metabolic stress leading to systemic inflammation and fibrosis. This is primarily due to diet-induced obesity. If you think about treating all of these competing risks to the patient’s life, the optimal way is to treat the root cause,” he said.

Various options exist to manage the conditions that can lead to NASH, but several of these also appear promising as a treatment of NASH, Dr. Sanyal said. Glucagonlike peptide–1 agonists and sodium-glucose transporter 2 inhibitors have been shown to improve multiple outcomes of interest in type 2 diabetes. However, insulin can cause weight gain at the expense of controlling HbA1C levels, he said.

Bariatric surgery can improve histology, but many patients with advanced fibrosis do not demonstrate improvement in fibrosis. Also, bariatric surgery has its own associated morbidity, including an increased suicide rate across multiple studies, Dr. Sanyal noted.

A new and interesting option is duodenal mucosal resurfacing (DMR) “a novel, minimally invasive outpatient upper-endoscopic procedure,” said Dr. Sanyal. DMR involves use of a catheter to perform a submucosal lift and hydrothermal mucosal ablation, prompting healthy epithelial regrowth, he explained. “The mucosa sloughs off, fresh epithelium grows in, and the hormonal signal from the gut to the rest of the body is restored to a more normal pattern,” he noted.

In the REVITA-2 study of patients with diabetes and NAFLD, the average fat loss was 5.4% in those randomized to DMR vs. 2.4% in sham-procedure patients and represented “quite significant defatting of the liver,” Dr. Sanyal said.

Dr. Sanyal then focused on fatty liver disease. “The first step when you see a patient with fatty liver disease is to see how scarred is the liver, and whether the patient has silent cirrhosis. The more scarred the liver, the greater risk of liver-related outcomes,” he said. The goal of therapy for these patients is to reduce the risk of progression to cirrhosis, he added. Dr. Sanyal recommended evaluating fibrosis using the Fibrosis 4 score (Fib4). “If the Fib4 is less than 1.3, the likelihood of significant scarring in the liver is less than 10%,” he said. On the other hand, a Fib4 greater than 2.67 suggests advanced fibrosis, he noted.

Overall, the goals of treatment for NASH patients are to prevent cirrhosis, reduce decompensation, and prevent hepatocellular carcinoma, said Dr. Sanyal.

“The ideal drug for NASH should also help other end organs, or at least be neutral,” said Dr. Sanyal.

Current frontline therapies for precirrhotic NASH include thiazolidinediones (TZD), farnesoid X receptor (FXR)/fibroblast growth factor 19 (FGF-19), FGF21, thyroxine B-R, and glucagonlike peptide-1. Clinical evidence varies based on different populations, endpoints, assessment methods, and treatment duration, he said.

Looking ahead to the next decade, a NASH management paradigm will likely play out that can be applied in the clinic today, Dr. Sanyal said. First, make an initial assessment of the status of the end organs. Start with a weight-loss regimen; use statins and GLP-1 and SGLT2 inhibitors as needed. Follow and reassess, and if the patient still has disease, progress to targeted therapy for active NASH while continuing to encourage weight loss and healthy living, he said.

“The ultimate proof that what we are doing is working is that we are improving mortality, reducing health care costs, and improving patients’ function and quality of life,” he concluded.

Dr. Sanyal is president of Sanyal Biotechnologies. He also disclosed stock options for Durect, Exhalenz, Galmed, Genfit, Immuton, Indalo, and Tiziana, as well as various relationships with Allergan, AMRA, Astra Zeneca-Medimmune, Birdrock, Boehringer Ingelheim, Bristol Myers, Echosense, GE, Genentech, Gilead, Hemoshear, IFMO, Innovate, Intercept, Lilly, Lipocine, Merck, Novartis, Novo Nordisk, OWL, Pfizer, RedX, Sundise, Tern, and Zydus.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Not only the prevalence, but the impact of nonalcoholic fatty liver disease (NAFLD) is increasing in much of the world, Arun J. Sanyal, MD, said in a virtual presentation at the meeting jointly provided by Rutgers and Global Academy for Medical Education. “It is currently estimated that the number of people living with cirrhosis or with decompensated cirrhosis will increase two- to threefold from 2015 to 2030,” which underlines the public health impact and the need for improved treatment paradigms, he emphasized.

“The thing to remember about NAFLD is that it does not exist in a vacuum,” Dr. Sanyal said. NAFLD is a multisystem disorder. Most patients have concomitant cardiovascular disease, but others may have type 2 diabetes, hypertension, and dyslipidemia, all of which are now accepted as risk factors for nonalcoholic steatohepatitis (NASH), he said.

“What ties these conditions together is metabolic stress leading to systemic inflammation and fibrosis. This is primarily due to diet-induced obesity. If you think about treating all of these competing risks to the patient’s life, the optimal way is to treat the root cause,” he said.

Various options exist to manage the conditions that can lead to NASH, but several of these also appear promising as a treatment of NASH, Dr. Sanyal said. Glucagonlike peptide–1 agonists and sodium-glucose transporter 2 inhibitors have been shown to improve multiple outcomes of interest in type 2 diabetes. However, insulin can cause weight gain at the expense of controlling HbA1C levels, he said.

Bariatric surgery can improve histology, but many patients with advanced fibrosis do not demonstrate improvement in fibrosis. Also, bariatric surgery has its own associated morbidity, including an increased suicide rate across multiple studies, Dr. Sanyal noted.

A new and interesting option is duodenal mucosal resurfacing (DMR) “a novel, minimally invasive outpatient upper-endoscopic procedure,” said Dr. Sanyal. DMR involves use of a catheter to perform a submucosal lift and hydrothermal mucosal ablation, prompting healthy epithelial regrowth, he explained. “The mucosa sloughs off, fresh epithelium grows in, and the hormonal signal from the gut to the rest of the body is restored to a more normal pattern,” he noted.

In the REVITA-2 study of patients with diabetes and NAFLD, the average fat loss was 5.4% in those randomized to DMR vs. 2.4% in sham-procedure patients and represented “quite significant defatting of the liver,” Dr. Sanyal said.

Dr. Sanyal then focused on fatty liver disease. “The first step when you see a patient with fatty liver disease is to see how scarred is the liver, and whether the patient has silent cirrhosis. The more scarred the liver, the greater risk of liver-related outcomes,” he said. The goal of therapy for these patients is to reduce the risk of progression to cirrhosis, he added. Dr. Sanyal recommended evaluating fibrosis using the Fibrosis 4 score (Fib4). “If the Fib4 is less than 1.3, the likelihood of significant scarring in the liver is less than 10%,” he said. On the other hand, a Fib4 greater than 2.67 suggests advanced fibrosis, he noted.

Overall, the goals of treatment for NASH patients are to prevent cirrhosis, reduce decompensation, and prevent hepatocellular carcinoma, said Dr. Sanyal.

“The ideal drug for NASH should also help other end organs, or at least be neutral,” said Dr. Sanyal.

Current frontline therapies for precirrhotic NASH include thiazolidinediones (TZD), farnesoid X receptor (FXR)/fibroblast growth factor 19 (FGF-19), FGF21, thyroxine B-R, and glucagonlike peptide-1. Clinical evidence varies based on different populations, endpoints, assessment methods, and treatment duration, he said.

Looking ahead to the next decade, a NASH management paradigm will likely play out that can be applied in the clinic today, Dr. Sanyal said. First, make an initial assessment of the status of the end organs. Start with a weight-loss regimen; use statins and GLP-1 and SGLT2 inhibitors as needed. Follow and reassess, and if the patient still has disease, progress to targeted therapy for active NASH while continuing to encourage weight loss and healthy living, he said.

“The ultimate proof that what we are doing is working is that we are improving mortality, reducing health care costs, and improving patients’ function and quality of life,” he concluded.

Dr. Sanyal is president of Sanyal Biotechnologies. He also disclosed stock options for Durect, Exhalenz, Galmed, Genfit, Immuton, Indalo, and Tiziana, as well as various relationships with Allergan, AMRA, Astra Zeneca-Medimmune, Birdrock, Boehringer Ingelheim, Bristol Myers, Echosense, GE, Genentech, Gilead, Hemoshear, IFMO, Innovate, Intercept, Lilly, Lipocine, Merck, Novartis, Novo Nordisk, OWL, Pfizer, RedX, Sundise, Tern, and Zydus.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Not only the prevalence, but the impact of nonalcoholic fatty liver disease (NAFLD) is increasing in much of the world, Arun J. Sanyal, MD, said in a virtual presentation at the meeting jointly provided by Rutgers and Global Academy for Medical Education. “It is currently estimated that the number of people living with cirrhosis or with decompensated cirrhosis will increase two- to threefold from 2015 to 2030,” which underlines the public health impact and the need for improved treatment paradigms, he emphasized.

“The thing to remember about NAFLD is that it does not exist in a vacuum,” Dr. Sanyal said. NAFLD is a multisystem disorder. Most patients have concomitant cardiovascular disease, but others may have type 2 diabetes, hypertension, and dyslipidemia, all of which are now accepted as risk factors for nonalcoholic steatohepatitis (NASH), he said.

“What ties these conditions together is metabolic stress leading to systemic inflammation and fibrosis. This is primarily due to diet-induced obesity. If you think about treating all of these competing risks to the patient’s life, the optimal way is to treat the root cause,” he said.

Various options exist to manage the conditions that can lead to NASH, but several of these also appear promising as a treatment of NASH, Dr. Sanyal said. Glucagonlike peptide–1 agonists and sodium-glucose transporter 2 inhibitors have been shown to improve multiple outcomes of interest in type 2 diabetes. However, insulin can cause weight gain at the expense of controlling HbA1C levels, he said.

Bariatric surgery can improve histology, but many patients with advanced fibrosis do not demonstrate improvement in fibrosis. Also, bariatric surgery has its own associated morbidity, including an increased suicide rate across multiple studies, Dr. Sanyal noted.

A new and interesting option is duodenal mucosal resurfacing (DMR) “a novel, minimally invasive outpatient upper-endoscopic procedure,” said Dr. Sanyal. DMR involves use of a catheter to perform a submucosal lift and hydrothermal mucosal ablation, prompting healthy epithelial regrowth, he explained. “The mucosa sloughs off, fresh epithelium grows in, and the hormonal signal from the gut to the rest of the body is restored to a more normal pattern,” he noted.

In the REVITA-2 study of patients with diabetes and NAFLD, the average fat loss was 5.4% in those randomized to DMR vs. 2.4% in sham-procedure patients and represented “quite significant defatting of the liver,” Dr. Sanyal said.

Dr. Sanyal then focused on fatty liver disease. “The first step when you see a patient with fatty liver disease is to see how scarred is the liver, and whether the patient has silent cirrhosis. The more scarred the liver, the greater risk of liver-related outcomes,” he said. The goal of therapy for these patients is to reduce the risk of progression to cirrhosis, he added. Dr. Sanyal recommended evaluating fibrosis using the Fibrosis 4 score (Fib4). “If the Fib4 is less than 1.3, the likelihood of significant scarring in the liver is less than 10%,” he said. On the other hand, a Fib4 greater than 2.67 suggests advanced fibrosis, he noted.

Overall, the goals of treatment for NASH patients are to prevent cirrhosis, reduce decompensation, and prevent hepatocellular carcinoma, said Dr. Sanyal.

“The ideal drug for NASH should also help other end organs, or at least be neutral,” said Dr. Sanyal.

Current frontline therapies for precirrhotic NASH include thiazolidinediones (TZD), farnesoid X receptor (FXR)/fibroblast growth factor 19 (FGF-19), FGF21, thyroxine B-R, and glucagonlike peptide-1. Clinical evidence varies based on different populations, endpoints, assessment methods, and treatment duration, he said.

Looking ahead to the next decade, a NASH management paradigm will likely play out that can be applied in the clinic today, Dr. Sanyal said. First, make an initial assessment of the status of the end organs. Start with a weight-loss regimen; use statins and GLP-1 and SGLT2 inhibitors as needed. Follow and reassess, and if the patient still has disease, progress to targeted therapy for active NASH while continuing to encourage weight loss and healthy living, he said.

“The ultimate proof that what we are doing is working is that we are improving mortality, reducing health care costs, and improving patients’ function and quality of life,” he concluded.

Dr. Sanyal is president of Sanyal Biotechnologies. He also disclosed stock options for Durect, Exhalenz, Galmed, Genfit, Immuton, Indalo, and Tiziana, as well as various relationships with Allergan, AMRA, Astra Zeneca-Medimmune, Birdrock, Boehringer Ingelheim, Bristol Myers, Echosense, GE, Genentech, Gilead, Hemoshear, IFMO, Innovate, Intercept, Lilly, Lipocine, Merck, Novartis, Novo Nordisk, OWL, Pfizer, RedX, Sundise, Tern, and Zydus.

Global Academy for Medical Education and this news organization are owned by the same parent company.

A Pesco-Mediterranean diet consisting of plants, legumes, nuts, whole grains, extra-virgin olive oil (EVOO), moderate amounts of dairy products, and fish and/or seafood, together with intermittent fasting (also called time-restricted eating), can reduce risk for cardiovascular disease (CVD), according to a new review.

The authors presented the research and conceptual underpinnings of this approach, which “proposes that following a Pesco-Mediterranean diet with time-restricted eating is evidence-based and ideal for reducing cardiovascular risk,” study coauthor Sarah Smith, PhD, RN, of Saint Luke’s Mid America Heart Institute, Kansas City, Mo., said in an interview.

The review was published online September 14 in the Journal of the American College of Cardiology.
 

‘Omnivore’s dilemma’

A host of epidemiologic studies and randomized clinical trials support an association between the traditional Mediterranean diet and lower risk for all-cause and CVD mortality, coronary heart disease, metabolic syndrome, neurodegenerative diseases, and other adverse outcome. The diet has been subsequently endorsed by several sets of guidelines, including those from the Department of Health & Human Services and the Department of Agriculture, and the 2019 American Heart Association/American College of Cardiology primary prevention guidelines.

“Although humans are omnivores and can subsist on a myriad of foods, the ideal diet for health remains a dilemma for many people,” lead author James H. O’Keefe, MD, director of preventive cardiology at Saint Luke’s, said in a news release.

“Plant-rich diets reduce CVD risk; however, veganism is difficult to follow and can result in important nutrient deficiencies,” he stated.

On the other hand, “the standard American diet is high in red meat, especially processed meat from animals raised in inhumane conditions, fed unnatural foods, and often treated with hormones and antibiotics,” the authors pointed out.

Together with overconsumption of red meat, sugar and processed food contribute to poor health outcomes, Dr. Smith noted.

The review was designed to present the Pesco-Mediterranean diet as “a solution to the ‘omnivore’s dilemma’ about what to eat,” said Dr. O’Keefe.

Study coauthor Ibrahim M. Saeed, MD, a cardiologist at Saint Luke’s, added that the research “attempts to emphasize the results of landmark prospective trials that highlight good, healthy eating options rather than just [foods that people would] want to avoid.”
 

Key components

The traditional Mediterranean diet includes “unrestricted use of EVOO,” but the quality of the olive oil is “crucial” and it must be unrefined and cold pressed, the authors emphasized.

The “highly bioactive” polyphenols likely “underlie EVOO’s numerous cardiometabolic benefits,” the researchers wrote, noting that the 2014 PREDIMED trial provided “first-level scientific evidence of [EVOO’s] cardioprotective effects [if used] within the context of the Mediterranean diet.”

The authors recommend “generous use” of EVOO in salad dressings and vegetable dishes, pasta, rice, fish, sauces, or legumes.

They also review the role of tree nuts, noting that they are “nutrient-dense foods rich in unsaturated fats, fiber, protein, polyphenols, phytosterols, tocopherols, and nonsodium minerals” and have been shown beneficial in CVD prevention.

Legumes play a “central role” in the Mediterranean diet and are an “excellent source” of vegetable protein, folate, magnesium, and fiber. Legume consumption is associated with lowered risk for CVD, as well as improved blood glucose, cholesterol, blood pressure, and body weight, the authors stated.

Whole grains like barley, whole oats, brown rice, and quinoa are likewise central components of the traditional Mediterranean diet. The authors warned that refined grain products and commercial precooked pasta or pizza should be “consumed only in small amounts.”
 

Window of time

In time-restricted eating (which is one type of intermittent fasting), the daily intake of food is limited to a window of time, usually 6-12 hours each day, the authors explained.

When done regularly, this type of eating has been shown to both decrease intra-abdominal adipose tissue and reduce free-radical production. Additionally, it “elicits powerful cellular responses” that may reduce risks for systemic inflammation, diabetes, CVD, cancer, and neurodegenerative diseases.

However, the authors warned, the evidence supporting time-restricted eating is still preliminary.
 

‘Let food be thy medicine’

Andrew Freeman, MD, cochair of the ACC’s nutrition & lifestyle work group, cautioned that many American plant-based Mediterranean diets often include large amount of feta cheese and lamb and foods are often “heavily doused” in olive oil, while the traditional Mediterranean diet consists primarily of greens and lentils and is plant based.

“The goal would be to have a whole grain and leafy vegetables as the center of the meal, and – if an animal product such as fish is included – it should be limited to as little as possible and used as the garnish rather than the main dish,” he stated.

Moreover, fish are often exposed to large amount of toxins, heavy metals, and microplastics, so “don’t overdo eating fish,” he advised.

Dr. Freeman said that intermittent fasting “has a lot of promise and no harm” and concentrating food consumption during a shorter period in the day instead of “grazing throughout the day” will reduce constant snacking. “But don’t gorge yourself during those hours,” he warned.

Dr. Freeman concluded by citing the guidance of Hippocrates: “Let food be thy medicine.

“There’s some real truth to that,” he added.

No source of funding was listed. Dr. Smith and Dr. Freeman disclosed no relevant financial relationships. Dr. O’Keefe has a major ownership interest in CardioTabs, a supplement company that sells some products containing omega-3 fatty acids.

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

A Pesco-Mediterranean diet consisting of plants, legumes, nuts, whole grains, extra-virgin olive oil (EVOO), moderate amounts of dairy products, and fish and/or seafood, together with intermittent fasting (also called time-restricted eating), can reduce risk for cardiovascular disease (CVD), according to a new review.

The authors presented the research and conceptual underpinnings of this approach, which “proposes that following a Pesco-Mediterranean diet with time-restricted eating is evidence-based and ideal for reducing cardiovascular risk,” study coauthor Sarah Smith, PhD, RN, of Saint Luke’s Mid America Heart Institute, Kansas City, Mo., said in an interview.

The review was published online September 14 in the Journal of the American College of Cardiology.
 

‘Omnivore’s dilemma’

A host of epidemiologic studies and randomized clinical trials support an association between the traditional Mediterranean diet and lower risk for all-cause and CVD mortality, coronary heart disease, metabolic syndrome, neurodegenerative diseases, and other adverse outcome. The diet has been subsequently endorsed by several sets of guidelines, including those from the Department of Health & Human Services and the Department of Agriculture, and the 2019 American Heart Association/American College of Cardiology primary prevention guidelines.

“Although humans are omnivores and can subsist on a myriad of foods, the ideal diet for health remains a dilemma for many people,” lead author James H. O’Keefe, MD, director of preventive cardiology at Saint Luke’s, said in a news release.

“Plant-rich diets reduce CVD risk; however, veganism is difficult to follow and can result in important nutrient deficiencies,” he stated.

On the other hand, “the standard American diet is high in red meat, especially processed meat from animals raised in inhumane conditions, fed unnatural foods, and often treated with hormones and antibiotics,” the authors pointed out.

Together with overconsumption of red meat, sugar and processed food contribute to poor health outcomes, Dr. Smith noted.

The review was designed to present the Pesco-Mediterranean diet as “a solution to the ‘omnivore’s dilemma’ about what to eat,” said Dr. O’Keefe.

Study coauthor Ibrahim M. Saeed, MD, a cardiologist at Saint Luke’s, added that the research “attempts to emphasize the results of landmark prospective trials that highlight good, healthy eating options rather than just [foods that people would] want to avoid.”
 

Key components

The traditional Mediterranean diet includes “unrestricted use of EVOO,” but the quality of the olive oil is “crucial” and it must be unrefined and cold pressed, the authors emphasized.

The “highly bioactive” polyphenols likely “underlie EVOO’s numerous cardiometabolic benefits,” the researchers wrote, noting that the 2014 PREDIMED trial provided “first-level scientific evidence of [EVOO’s] cardioprotective effects [if used] within the context of the Mediterranean diet.”

The authors recommend “generous use” of EVOO in salad dressings and vegetable dishes, pasta, rice, fish, sauces, or legumes.

They also review the role of tree nuts, noting that they are “nutrient-dense foods rich in unsaturated fats, fiber, protein, polyphenols, phytosterols, tocopherols, and nonsodium minerals” and have been shown beneficial in CVD prevention.

Legumes play a “central role” in the Mediterranean diet and are an “excellent source” of vegetable protein, folate, magnesium, and fiber. Legume consumption is associated with lowered risk for CVD, as well as improved blood glucose, cholesterol, blood pressure, and body weight, the authors stated.

Whole grains like barley, whole oats, brown rice, and quinoa are likewise central components of the traditional Mediterranean diet. The authors warned that refined grain products and commercial precooked pasta or pizza should be “consumed only in small amounts.”
 

Window of time

In time-restricted eating (which is one type of intermittent fasting), the daily intake of food is limited to a window of time, usually 6-12 hours each day, the authors explained.

When done regularly, this type of eating has been shown to both decrease intra-abdominal adipose tissue and reduce free-radical production. Additionally, it “elicits powerful cellular responses” that may reduce risks for systemic inflammation, diabetes, CVD, cancer, and neurodegenerative diseases.

However, the authors warned, the evidence supporting time-restricted eating is still preliminary.
 

‘Let food be thy medicine’

Andrew Freeman, MD, cochair of the ACC’s nutrition & lifestyle work group, cautioned that many American plant-based Mediterranean diets often include large amount of feta cheese and lamb and foods are often “heavily doused” in olive oil, while the traditional Mediterranean diet consists primarily of greens and lentils and is plant based.

“The goal would be to have a whole grain and leafy vegetables as the center of the meal, and – if an animal product such as fish is included – it should be limited to as little as possible and used as the garnish rather than the main dish,” he stated.

Moreover, fish are often exposed to large amount of toxins, heavy metals, and microplastics, so “don’t overdo eating fish,” he advised.

Dr. Freeman said that intermittent fasting “has a lot of promise and no harm” and concentrating food consumption during a shorter period in the day instead of “grazing throughout the day” will reduce constant snacking. “But don’t gorge yourself during those hours,” he warned.

Dr. Freeman concluded by citing the guidance of Hippocrates: “Let food be thy medicine.

“There’s some real truth to that,” he added.

No source of funding was listed. Dr. Smith and Dr. Freeman disclosed no relevant financial relationships. Dr. O’Keefe has a major ownership interest in CardioTabs, a supplement company that sells some products containing omega-3 fatty acids.

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

A Pesco-Mediterranean diet consisting of plants, legumes, nuts, whole grains, extra-virgin olive oil (EVOO), moderate amounts of dairy products, and fish and/or seafood, together with intermittent fasting (also called time-restricted eating), can reduce risk for cardiovascular disease (CVD), according to a new review.

The authors presented the research and conceptual underpinnings of this approach, which “proposes that following a Pesco-Mediterranean diet with time-restricted eating is evidence-based and ideal for reducing cardiovascular risk,” study coauthor Sarah Smith, PhD, RN, of Saint Luke’s Mid America Heart Institute, Kansas City, Mo., said in an interview.

The review was published online September 14 in the Journal of the American College of Cardiology.
 

‘Omnivore’s dilemma’

A host of epidemiologic studies and randomized clinical trials support an association between the traditional Mediterranean diet and lower risk for all-cause and CVD mortality, coronary heart disease, metabolic syndrome, neurodegenerative diseases, and other adverse outcome. The diet has been subsequently endorsed by several sets of guidelines, including those from the Department of Health & Human Services and the Department of Agriculture, and the 2019 American Heart Association/American College of Cardiology primary prevention guidelines.

“Although humans are omnivores and can subsist on a myriad of foods, the ideal diet for health remains a dilemma for many people,” lead author James H. O’Keefe, MD, director of preventive cardiology at Saint Luke’s, said in a news release.

“Plant-rich diets reduce CVD risk; however, veganism is difficult to follow and can result in important nutrient deficiencies,” he stated.

On the other hand, “the standard American diet is high in red meat, especially processed meat from animals raised in inhumane conditions, fed unnatural foods, and often treated with hormones and antibiotics,” the authors pointed out.

Together with overconsumption of red meat, sugar and processed food contribute to poor health outcomes, Dr. Smith noted.

The review was designed to present the Pesco-Mediterranean diet as “a solution to the ‘omnivore’s dilemma’ about what to eat,” said Dr. O’Keefe.

Study coauthor Ibrahim M. Saeed, MD, a cardiologist at Saint Luke’s, added that the research “attempts to emphasize the results of landmark prospective trials that highlight good, healthy eating options rather than just [foods that people would] want to avoid.”
 

Key components

The traditional Mediterranean diet includes “unrestricted use of EVOO,” but the quality of the olive oil is “crucial” and it must be unrefined and cold pressed, the authors emphasized.

The “highly bioactive” polyphenols likely “underlie EVOO’s numerous cardiometabolic benefits,” the researchers wrote, noting that the 2014 PREDIMED trial provided “first-level scientific evidence of [EVOO’s] cardioprotective effects [if used] within the context of the Mediterranean diet.”

The authors recommend “generous use” of EVOO in salad dressings and vegetable dishes, pasta, rice, fish, sauces, or legumes.

They also review the role of tree nuts, noting that they are “nutrient-dense foods rich in unsaturated fats, fiber, protein, polyphenols, phytosterols, tocopherols, and nonsodium minerals” and have been shown beneficial in CVD prevention.

Legumes play a “central role” in the Mediterranean diet and are an “excellent source” of vegetable protein, folate, magnesium, and fiber. Legume consumption is associated with lowered risk for CVD, as well as improved blood glucose, cholesterol, blood pressure, and body weight, the authors stated.

Whole grains like barley, whole oats, brown rice, and quinoa are likewise central components of the traditional Mediterranean diet. The authors warned that refined grain products and commercial precooked pasta or pizza should be “consumed only in small amounts.”
 

Window of time

In time-restricted eating (which is one type of intermittent fasting), the daily intake of food is limited to a window of time, usually 6-12 hours each day, the authors explained.

When done regularly, this type of eating has been shown to both decrease intra-abdominal adipose tissue and reduce free-radical production. Additionally, it “elicits powerful cellular responses” that may reduce risks for systemic inflammation, diabetes, CVD, cancer, and neurodegenerative diseases.

However, the authors warned, the evidence supporting time-restricted eating is still preliminary.
 

‘Let food be thy medicine’

Andrew Freeman, MD, cochair of the ACC’s nutrition & lifestyle work group, cautioned that many American plant-based Mediterranean diets often include large amount of feta cheese and lamb and foods are often “heavily doused” in olive oil, while the traditional Mediterranean diet consists primarily of greens and lentils and is plant based.

“The goal would be to have a whole grain and leafy vegetables as the center of the meal, and – if an animal product such as fish is included – it should be limited to as little as possible and used as the garnish rather than the main dish,” he stated.

Moreover, fish are often exposed to large amount of toxins, heavy metals, and microplastics, so “don’t overdo eating fish,” he advised.

Dr. Freeman said that intermittent fasting “has a lot of promise and no harm” and concentrating food consumption during a shorter period in the day instead of “grazing throughout the day” will reduce constant snacking. “But don’t gorge yourself during those hours,” he warned.

Dr. Freeman concluded by citing the guidance of Hippocrates: “Let food be thy medicine.

“There’s some real truth to that,” he added.

No source of funding was listed. Dr. Smith and Dr. Freeman disclosed no relevant financial relationships. Dr. O’Keefe has a major ownership interest in CardioTabs, a supplement company that sells some products containing omega-3 fatty acids.

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

New guidelines on sports cardiology from the European Society of Cardiology break fresh ground by green-lighting participation in vigorous competitive sports by selected patients with stable coronary artery disease, heart failure, or mild arrhythmias.

These liberalized guidelines, released at the virtual annual congress of the European Society of Cardiology, thus move well beyond the standard exercise advice to engage in about 150 minutes per week of moderate physical activity, typically defined as brisk walking or its equivalent.

The guidelines reflect a conviction that exercise is powerful medicine for patients with cardiovascular disease and also affords a means to help curb the epidemics of diabetes and obesity that drive cardiovascular risk, according to Antonio Pelliccia, MD, who cochaired the 24-member task force of European and American experts that developed the guidelines.

In a session highlighting the new sports cardiology guidelines, Mats Borjesson, MD, head of the Center for Health and Performance at Gothenburg (Sweden) University, summarized the section devoted to patients with stable coronary artery disease: “If you have established CAD and a low risk of adverse events during exercise, you are eligible for high-intensity exercise and competitive sports. But if you have persistent ischemia despite medical treatment, or symptoms, then you’re only eligible for leisure-time subthreshold activity.”

Dr. Pelliccia put this new recommendation into context.

“We are not talking anymore in this particular disease just about cardiac rehabilitation or leisure-time activity, but we are also opening the border and talking about competitive sports activity in selected patients where you have the evidence for low risk of exercise-induced adverse events. This is a major achievement now for what is the major disease in our adult population,” said Dr. Pelliccia, chief of cardiology at the Institute of Sports Medicine and Science at the Italian National Olympic Committee and professor of sports cardiology at La Sapienza University of Rome.

The recommendation for individualized consideration of all types of exercise, even including vigorous competitive sports, in low-risk patients with CAD gets a class IIa, level of evidence (LOE) C recommendation in the new guidelines. That’s a big step down from a ringing class Ia endorsement, but since sports cardiology is a relatively young field with little evidence that’s based on randomized trials, the guidelines are rife with many other class IIa, LOE C recommendations as well.

“The level of evidence is rather low, so these guidelines are very much the personal perspective of the expert panel,” explained Martin Halle, MD, professor and head of the department of prevention, rehabilitation, and sports cardiology at Technical University of Munich.

The high-risk features for exercise-induced cardiac adverse events in patients with longstanding stable CAD, as cited in the guidelines, include a critical coronary stenosis, defined as a more than 70% lesion in a major coronary artery or a greater than 50% stenosis in the left main, and/or a fractional flow reserve score of less than 0.8; a left ventricular ejection fraction of 50% or less with wall-motion abnormalities; inducible myocardial ischemia on maximal exercise testing; nonsustained ventricular tachycardia; polymorphic or very frequent ventricular premature beats at rest and during maximum stress; and a recent acute coronary syndrome (ACS). These features call for an exercise prescription tailored to remain below the patient’s angina and ischemia thresholds.

“It’s important for cardiologists out there to understand that we definitely need a maximal exercise test. In somebody who is running and has an ACS and then wants to start running again, 200 watts on an ergometer is too low. We have to push them up to the end, and then if everything is okay – left ventricular function is okay, no ischemia, no arrhythmias under exercise testing – then it’s fine,” Dr. Halle said.

Dr. Pelliccia added that close follow-up is needed, because this is an evolving disease.”
 

Exercise and heart failure

Massimo F. Piepoli, MD, PhD, noted that the guidelines give a class IIb, LOE C recommendation for consideration of high-intensity recreational endurance and power sports in patients with heart failure with either midrange or preserved ejection fraction, provided they are stable, asymptomatic, on optimal guideline-directed medical therapy, and without abnormalities on a maximal exercise stress test.

European Society of Cardiology

However, such intense physical activity is not recommended in patients with heart failure with reduced ejection fraction, regardless of their symptom status, added Dr. Piepoli of Guglielmo da Saliceto Hospital in Placenza, Italy.

“We’re talking here, I think for the first time, about possible competitive sports participation in individuals with heart failure, depending on their clinical condition. We are really opening the barriers to sports participation, even in these patients in whom we never thought of it before,” Dr. Pelliccia observed.

Valvular heart disease and exercise

Guidelines panelist Sabiha Gati, MRCP, PhD, said asymptomatic individuals with mild valvular abnormalities can participate in all recreational and competitive sports; that’s a class I, LOE C recommendation.

European Society of Cardiology

“Moderate regurgitant lesions are better tolerated than stenotic lesions, and those with preserved systolic function, good functional capacity, without any exercise-induced arrhythmias or ischemia or abnormal hemodynamic response are considered to be low risk and can participate in all sports,” added Dr. Gati, a cardiologist at Royal Brompton Hospital, London.

The two most common valvular abnormalities encountered in clinical practice are bicuspid aortic valve and mitral valve prolapse. Dr. Gati noted that, while mitral valve prolapse has a benign prognosis in the great majority of affected individuals, the presence of specific features indicative of increased risk for sudden cardiac death precludes participation in strenuous exercise. These include T-wave inversion in the inferior leads on a 12-lead ECG, long QT, bileaflet mitral valve prolapse, basal inferolateral wall fibrosis, severe mitral regurgitation, or a family history of sudden cardiac death.

Bicuspid aortic valve has a prevalence of 1%-2% in the general population. It can be associated with aortic stenosis, aortic regurgitation, and increased risk of ascending aortic aneurysm and dissection. Since it remains unclear whether intensive exercise accelerates aortic dilatation, a cautious approach to sports participation is recommended in patients with an ascending aorta above the normal limit of 40 mm, she said.

The 80-page ESC sports cardiology guidelines, published online simultaneously with their presentation, cover a broad range of additional topics, including exercise recommendations for the general public, for the elderly, as well as for patients with cardiomyopathies, adult congenital heart disease, arrhythmias, and channelopathies. Gaps in evidence are also highlighted.

[email protected]

SOURCE: Pelliccia A. ESC 2020 and Eur Heart J. 2020 Aug 29. doi: 10.1093/eurheartj/ehaa605.

New guidelines on sports cardiology from the European Society of Cardiology break fresh ground by green-lighting participation in vigorous competitive sports by selected patients with stable coronary artery disease, heart failure, or mild arrhythmias.

These liberalized guidelines, released at the virtual annual congress of the European Society of Cardiology, thus move well beyond the standard exercise advice to engage in about 150 minutes per week of moderate physical activity, typically defined as brisk walking or its equivalent.

The guidelines reflect a conviction that exercise is powerful medicine for patients with cardiovascular disease and also affords a means to help curb the epidemics of diabetes and obesity that drive cardiovascular risk, according to Antonio Pelliccia, MD, who cochaired the 24-member task force of European and American experts that developed the guidelines.

In a session highlighting the new sports cardiology guidelines, Mats Borjesson, MD, head of the Center for Health and Performance at Gothenburg (Sweden) University, summarized the section devoted to patients with stable coronary artery disease: “If you have established CAD and a low risk of adverse events during exercise, you are eligible for high-intensity exercise and competitive sports. But if you have persistent ischemia despite medical treatment, or symptoms, then you’re only eligible for leisure-time subthreshold activity.”

Dr. Pelliccia put this new recommendation into context.

“We are not talking anymore in this particular disease just about cardiac rehabilitation or leisure-time activity, but we are also opening the border and talking about competitive sports activity in selected patients where you have the evidence for low risk of exercise-induced adverse events. This is a major achievement now for what is the major disease in our adult population,” said Dr. Pelliccia, chief of cardiology at the Institute of Sports Medicine and Science at the Italian National Olympic Committee and professor of sports cardiology at La Sapienza University of Rome.

The recommendation for individualized consideration of all types of exercise, even including vigorous competitive sports, in low-risk patients with CAD gets a class IIa, level of evidence (LOE) C recommendation in the new guidelines. That’s a big step down from a ringing class Ia endorsement, but since sports cardiology is a relatively young field with little evidence that’s based on randomized trials, the guidelines are rife with many other class IIa, LOE C recommendations as well.

“The level of evidence is rather low, so these guidelines are very much the personal perspective of the expert panel,” explained Martin Halle, MD, professor and head of the department of prevention, rehabilitation, and sports cardiology at Technical University of Munich.

The high-risk features for exercise-induced cardiac adverse events in patients with longstanding stable CAD, as cited in the guidelines, include a critical coronary stenosis, defined as a more than 70% lesion in a major coronary artery or a greater than 50% stenosis in the left main, and/or a fractional flow reserve score of less than 0.8; a left ventricular ejection fraction of 50% or less with wall-motion abnormalities; inducible myocardial ischemia on maximal exercise testing; nonsustained ventricular tachycardia; polymorphic or very frequent ventricular premature beats at rest and during maximum stress; and a recent acute coronary syndrome (ACS). These features call for an exercise prescription tailored to remain below the patient’s angina and ischemia thresholds.

“It’s important for cardiologists out there to understand that we definitely need a maximal exercise test. In somebody who is running and has an ACS and then wants to start running again, 200 watts on an ergometer is too low. We have to push them up to the end, and then if everything is okay – left ventricular function is okay, no ischemia, no arrhythmias under exercise testing – then it’s fine,” Dr. Halle said.

Dr. Pelliccia added that close follow-up is needed, because this is an evolving disease.”
 

Exercise and heart failure

Massimo F. Piepoli, MD, PhD, noted that the guidelines give a class IIb, LOE C recommendation for consideration of high-intensity recreational endurance and power sports in patients with heart failure with either midrange or preserved ejection fraction, provided they are stable, asymptomatic, on optimal guideline-directed medical therapy, and without abnormalities on a maximal exercise stress test.

European Society of Cardiology

However, such intense physical activity is not recommended in patients with heart failure with reduced ejection fraction, regardless of their symptom status, added Dr. Piepoli of Guglielmo da Saliceto Hospital in Placenza, Italy.

“We’re talking here, I think for the first time, about possible competitive sports participation in individuals with heart failure, depending on their clinical condition. We are really opening the barriers to sports participation, even in these patients in whom we never thought of it before,” Dr. Pelliccia observed.

Valvular heart disease and exercise

Guidelines panelist Sabiha Gati, MRCP, PhD, said asymptomatic individuals with mild valvular abnormalities can participate in all recreational and competitive sports; that’s a class I, LOE C recommendation.

European Society of Cardiology

“Moderate regurgitant lesions are better tolerated than stenotic lesions, and those with preserved systolic function, good functional capacity, without any exercise-induced arrhythmias or ischemia or abnormal hemodynamic response are considered to be low risk and can participate in all sports,” added Dr. Gati, a cardiologist at Royal Brompton Hospital, London.

The two most common valvular abnormalities encountered in clinical practice are bicuspid aortic valve and mitral valve prolapse. Dr. Gati noted that, while mitral valve prolapse has a benign prognosis in the great majority of affected individuals, the presence of specific features indicative of increased risk for sudden cardiac death precludes participation in strenuous exercise. These include T-wave inversion in the inferior leads on a 12-lead ECG, long QT, bileaflet mitral valve prolapse, basal inferolateral wall fibrosis, severe mitral regurgitation, or a family history of sudden cardiac death.

Bicuspid aortic valve has a prevalence of 1%-2% in the general population. It can be associated with aortic stenosis, aortic regurgitation, and increased risk of ascending aortic aneurysm and dissection. Since it remains unclear whether intensive exercise accelerates aortic dilatation, a cautious approach to sports participation is recommended in patients with an ascending aorta above the normal limit of 40 mm, she said.

The 80-page ESC sports cardiology guidelines, published online simultaneously with their presentation, cover a broad range of additional topics, including exercise recommendations for the general public, for the elderly, as well as for patients with cardiomyopathies, adult congenital heart disease, arrhythmias, and channelopathies. Gaps in evidence are also highlighted.

[email protected]

SOURCE: Pelliccia A. ESC 2020 and Eur Heart J. 2020 Aug 29. doi: 10.1093/eurheartj/ehaa605.

New guidelines on sports cardiology from the European Society of Cardiology break fresh ground by green-lighting participation in vigorous competitive sports by selected patients with stable coronary artery disease, heart failure, or mild arrhythmias.

These liberalized guidelines, released at the virtual annual congress of the European Society of Cardiology, thus move well beyond the standard exercise advice to engage in about 150 minutes per week of moderate physical activity, typically defined as brisk walking or its equivalent.

The guidelines reflect a conviction that exercise is powerful medicine for patients with cardiovascular disease and also affords a means to help curb the epidemics of diabetes and obesity that drive cardiovascular risk, according to Antonio Pelliccia, MD, who cochaired the 24-member task force of European and American experts that developed the guidelines.

In a session highlighting the new sports cardiology guidelines, Mats Borjesson, MD, head of the Center for Health and Performance at Gothenburg (Sweden) University, summarized the section devoted to patients with stable coronary artery disease: “If you have established CAD and a low risk of adverse events during exercise, you are eligible for high-intensity exercise and competitive sports. But if you have persistent ischemia despite medical treatment, or symptoms, then you’re only eligible for leisure-time subthreshold activity.”

Dr. Pelliccia put this new recommendation into context.

“We are not talking anymore in this particular disease just about cardiac rehabilitation or leisure-time activity, but we are also opening the border and talking about competitive sports activity in selected patients where you have the evidence for low risk of exercise-induced adverse events. This is a major achievement now for what is the major disease in our adult population,” said Dr. Pelliccia, chief of cardiology at the Institute of Sports Medicine and Science at the Italian National Olympic Committee and professor of sports cardiology at La Sapienza University of Rome.

The recommendation for individualized consideration of all types of exercise, even including vigorous competitive sports, in low-risk patients with CAD gets a class IIa, level of evidence (LOE) C recommendation in the new guidelines. That’s a big step down from a ringing class Ia endorsement, but since sports cardiology is a relatively young field with little evidence that’s based on randomized trials, the guidelines are rife with many other class IIa, LOE C recommendations as well.

“The level of evidence is rather low, so these guidelines are very much the personal perspective of the expert panel,” explained Martin Halle, MD, professor and head of the department of prevention, rehabilitation, and sports cardiology at Technical University of Munich.

The high-risk features for exercise-induced cardiac adverse events in patients with longstanding stable CAD, as cited in the guidelines, include a critical coronary stenosis, defined as a more than 70% lesion in a major coronary artery or a greater than 50% stenosis in the left main, and/or a fractional flow reserve score of less than 0.8; a left ventricular ejection fraction of 50% or less with wall-motion abnormalities; inducible myocardial ischemia on maximal exercise testing; nonsustained ventricular tachycardia; polymorphic or very frequent ventricular premature beats at rest and during maximum stress; and a recent acute coronary syndrome (ACS). These features call for an exercise prescription tailored to remain below the patient’s angina and ischemia thresholds.

“It’s important for cardiologists out there to understand that we definitely need a maximal exercise test. In somebody who is running and has an ACS and then wants to start running again, 200 watts on an ergometer is too low. We have to push them up to the end, and then if everything is okay – left ventricular function is okay, no ischemia, no arrhythmias under exercise testing – then it’s fine,” Dr. Halle said.

Dr. Pelliccia added that close follow-up is needed, because this is an evolving disease.”
 

Exercise and heart failure

Massimo F. Piepoli, MD, PhD, noted that the guidelines give a class IIb, LOE C recommendation for consideration of high-intensity recreational endurance and power sports in patients with heart failure with either midrange or preserved ejection fraction, provided they are stable, asymptomatic, on optimal guideline-directed medical therapy, and without abnormalities on a maximal exercise stress test.

European Society of Cardiology

However, such intense physical activity is not recommended in patients with heart failure with reduced ejection fraction, regardless of their symptom status, added Dr. Piepoli of Guglielmo da Saliceto Hospital in Placenza, Italy.

“We’re talking here, I think for the first time, about possible competitive sports participation in individuals with heart failure, depending on their clinical condition. We are really opening the barriers to sports participation, even in these patients in whom we never thought of it before,” Dr. Pelliccia observed.

Valvular heart disease and exercise

Guidelines panelist Sabiha Gati, MRCP, PhD, said asymptomatic individuals with mild valvular abnormalities can participate in all recreational and competitive sports; that’s a class I, LOE C recommendation.

European Society of Cardiology

“Moderate regurgitant lesions are better tolerated than stenotic lesions, and those with preserved systolic function, good functional capacity, without any exercise-induced arrhythmias or ischemia or abnormal hemodynamic response are considered to be low risk and can participate in all sports,” added Dr. Gati, a cardiologist at Royal Brompton Hospital, London.

The two most common valvular abnormalities encountered in clinical practice are bicuspid aortic valve and mitral valve prolapse. Dr. Gati noted that, while mitral valve prolapse has a benign prognosis in the great majority of affected individuals, the presence of specific features indicative of increased risk for sudden cardiac death precludes participation in strenuous exercise. These include T-wave inversion in the inferior leads on a 12-lead ECG, long QT, bileaflet mitral valve prolapse, basal inferolateral wall fibrosis, severe mitral regurgitation, or a family history of sudden cardiac death.

Bicuspid aortic valve has a prevalence of 1%-2% in the general population. It can be associated with aortic stenosis, aortic regurgitation, and increased risk of ascending aortic aneurysm and dissection. Since it remains unclear whether intensive exercise accelerates aortic dilatation, a cautious approach to sports participation is recommended in patients with an ascending aorta above the normal limit of 40 mm, she said.

The 80-page ESC sports cardiology guidelines, published online simultaneously with their presentation, cover a broad range of additional topics, including exercise recommendations for the general public, for the elderly, as well as for patients with cardiomyopathies, adult congenital heart disease, arrhythmias, and channelopathies. Gaps in evidence are also highlighted.

[email protected]

SOURCE: Pelliccia A. ESC 2020 and Eur Heart J. 2020 Aug 29. doi: 10.1093/eurheartj/ehaa605.

Biologics used as treatment for psoriasis may also help reduce lipid-rich necrotic core (LRNC), a high-risk plaque associated with cardiovascular events, recent research from a prospective, observational study suggests.

Waldemarus/Thinkstock

Cardiac CT scans performed on patients with psoriasis 1 year after starting biologic therapy revealed a reduction in LRNC, compared with patients who were not receiving biologics, according to Harry Choi, MD, of the National Heart, Lung, and Blood Institute at the National Institutes of Health and colleagues. The association with reduction in LRNC and biologic therapy remained significant when adjusted for type of biologic. “These findings demonstrate that LRNC may be modulated by the control of systemic inflammation,” the researchers wrote in their study, published Sept. 15 in Circulation: Cardiovascular Imaging.

Dr. Choi and colleagues evaluated 289 patients with psoriasis within the Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative cohort. The patients had a mean age of 50 years and a mean body mass index of 29.4 kg/m², as well as a mean Psoriasis Area and Severity Index (PASI) score of 6.0. At baseline, 29% of patients had hypertension, 41% had hyperlipidemia, their mean Framingham risk score was 1.9, and a three-quarters (212 of 289) had mild to moderate psoriasis.

Changes in LRNC were observed at 1 year, compared with baseline prior to and after receiving biologic therapy (124 patients) in comparison with patients who did not undergo biologic therapy (85 patients). Biologic therapies were grouped by type, which included anti–tumor necrosis factor (anti-TNF), anti–interleukin (IL)–12/23, and anti–IL-17 biologics.

There were a significant associations between LRNC and Framingham risk score (standardized beta coefficient, 0.12; 95% confidence interval, 0.00-0.15; P = .045) and severity of psoriasis (beta, 0.13; 95% CI, 0.01-0.26; P = .029) at baseline.
 

Key findings

The researchers found a significant reduction in LRNC 1 year after patients began biologic therapy (median, 2.97 mm²; interquartile range, 1.99-4.66), compared with baseline (median, 3.12 mm²; IQR, 1.84-4.35) (P = .028), while patients who did not receive biologic therapy had nonsignificantly higher LRNC after 1 year (median, 3.12 mm²; IQR, 1.82-4.60), compared with baseline measurements (median, 3.34 mm²; IQR, 2.04–4.74) (P = .06).

The results remained significant after the researchers adjusted for psoriasis severity, Framingham risk score, BMI, use of statins (beta, −0.09; 95% CI, −0.01 to −0.18; P = .033). Significant reductions in LRNC also remained when analyzing patients receiving anti-TNF, anti–IL-12/23, and anti–IL-17 biologics independently, and there were no significant between-group differences in reduction of LRNC.
 

The potential of biologics for improving vascular health

Discussing the study results in a press release from the American Heart Association, senior author Nehal N. Mehta, MD, MSCE, FAHA, chief of the Lab of Inflammation and Cardiometabolic Diseases at the NHLBI at NIH, compared the effect biologic therapy had on coronary plaque reduction with that of statins.

“There is approximately 6%-8% reduction in coronary plaque following therapy with statins. Similarly, our treatment with biologic therapy reduced coronary plaque by the same amount after one year. These findings suggest that biologic therapy to treat psoriasis may be just as beneficial as statin therapy on heart arteries,” Dr. Mehta said in the release.

In an interview, Nieca Goldberg, MD, medical director of NYU Women’s Heart Program at NYU Langone Health, echoed Dr. Mehta’s commments and said psoriasis carries the “potential to treat two conditions with the same drug.”

“We know conditions such as psoriatic arthritis and rheumatoid arthritis cause chronic inflammation. Chronic inflammation causes injury to blood vessels and high-risk coronary plaque. Individuals with these inflammatory conditions are at high risk for heart attack,” she said. “This study shows that biologic treatment for psoriatic arthritis can reduce the presence of high-risk plaque. It shows the potential to treat chronic inflammation and high-risk coronary plaque.”

While the results show an association between use of biologics and LRNC reduction, the study design was observational and patients had a short follow-up period. Dr. Goldberg noted more studies are needed to evaluate the effect of biologics on reducing cardiovascular events such as a myocardial infarction.

“We have never before been able to show healing of an inflamed plaque like this in humans. Biologic therapy reduces systemic inflammation and immune activation, and it has a favorable impact on improving overall vascular health,” Dr. Mehta said in the press release. “Imagine if we can treat both psoriasis and coronary heart disease with one therapy – that is the question to be asked in future studies.”

This study was funded with support from the NHLBI Intramural Research Program and the NIH Medical Research Scholars Program at the National Institutes of Health. One investigator reports financial relationships with numerous pharmaceutical companies. The other authors report no relevant conflicts of interest. Dr. Mehta also reports numerous such relationships. Dr. Goldberg reports no relevant conflicts of interest.

SOURCE: Choi H et al. Circ Cardiovasc Imaging. 2020 Sep;13(9):e011199.

Biologics used as treatment for psoriasis may also help reduce lipid-rich necrotic core (LRNC), a high-risk plaque associated with cardiovascular events, recent research from a prospective, observational study suggests.

Waldemarus/Thinkstock

Cardiac CT scans performed on patients with psoriasis 1 year after starting biologic therapy revealed a reduction in LRNC, compared with patients who were not receiving biologics, according to Harry Choi, MD, of the National Heart, Lung, and Blood Institute at the National Institutes of Health and colleagues. The association with reduction in LRNC and biologic therapy remained significant when adjusted for type of biologic. “These findings demonstrate that LRNC may be modulated by the control of systemic inflammation,” the researchers wrote in their study, published Sept. 15 in Circulation: Cardiovascular Imaging.

Dr. Choi and colleagues evaluated 289 patients with psoriasis within the Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative cohort. The patients had a mean age of 50 years and a mean body mass index of 29.4 kg/m², as well as a mean Psoriasis Area and Severity Index (PASI) score of 6.0. At baseline, 29% of patients had hypertension, 41% had hyperlipidemia, their mean Framingham risk score was 1.9, and a three-quarters (212 of 289) had mild to moderate psoriasis.

Changes in LRNC were observed at 1 year, compared with baseline prior to and after receiving biologic therapy (124 patients) in comparison with patients who did not undergo biologic therapy (85 patients). Biologic therapies were grouped by type, which included anti–tumor necrosis factor (anti-TNF), anti–interleukin (IL)–12/23, and anti–IL-17 biologics.

There were a significant associations between LRNC and Framingham risk score (standardized beta coefficient, 0.12; 95% confidence interval, 0.00-0.15; P = .045) and severity of psoriasis (beta, 0.13; 95% CI, 0.01-0.26; P = .029) at baseline.
 

Key findings

The researchers found a significant reduction in LRNC 1 year after patients began biologic therapy (median, 2.97 mm²; interquartile range, 1.99-4.66), compared with baseline (median, 3.12 mm²; IQR, 1.84-4.35) (P = .028), while patients who did not receive biologic therapy had nonsignificantly higher LRNC after 1 year (median, 3.12 mm²; IQR, 1.82-4.60), compared with baseline measurements (median, 3.34 mm²; IQR, 2.04–4.74) (P = .06).

The results remained significant after the researchers adjusted for psoriasis severity, Framingham risk score, BMI, use of statins (beta, −0.09; 95% CI, −0.01 to −0.18; P = .033). Significant reductions in LRNC also remained when analyzing patients receiving anti-TNF, anti–IL-12/23, and anti–IL-17 biologics independently, and there were no significant between-group differences in reduction of LRNC.
 

The potential of biologics for improving vascular health

Discussing the study results in a press release from the American Heart Association, senior author Nehal N. Mehta, MD, MSCE, FAHA, chief of the Lab of Inflammation and Cardiometabolic Diseases at the NHLBI at NIH, compared the effect biologic therapy had on coronary plaque reduction with that of statins.

“There is approximately 6%-8% reduction in coronary plaque following therapy with statins. Similarly, our treatment with biologic therapy reduced coronary plaque by the same amount after one year. These findings suggest that biologic therapy to treat psoriasis may be just as beneficial as statin therapy on heart arteries,” Dr. Mehta said in the release.

In an interview, Nieca Goldberg, MD, medical director of NYU Women’s Heart Program at NYU Langone Health, echoed Dr. Mehta’s commments and said psoriasis carries the “potential to treat two conditions with the same drug.”

“We know conditions such as psoriatic arthritis and rheumatoid arthritis cause chronic inflammation. Chronic inflammation causes injury to blood vessels and high-risk coronary plaque. Individuals with these inflammatory conditions are at high risk for heart attack,” she said. “This study shows that biologic treatment for psoriatic arthritis can reduce the presence of high-risk plaque. It shows the potential to treat chronic inflammation and high-risk coronary plaque.”

While the results show an association between use of biologics and LRNC reduction, the study design was observational and patients had a short follow-up period. Dr. Goldberg noted more studies are needed to evaluate the effect of biologics on reducing cardiovascular events such as a myocardial infarction.

“We have never before been able to show healing of an inflamed plaque like this in humans. Biologic therapy reduces systemic inflammation and immune activation, and it has a favorable impact on improving overall vascular health,” Dr. Mehta said in the press release. “Imagine if we can treat both psoriasis and coronary heart disease with one therapy – that is the question to be asked in future studies.”

This study was funded with support from the NHLBI Intramural Research Program and the NIH Medical Research Scholars Program at the National Institutes of Health. One investigator reports financial relationships with numerous pharmaceutical companies. The other authors report no relevant conflicts of interest. Dr. Mehta also reports numerous such relationships. Dr. Goldberg reports no relevant conflicts of interest.

SOURCE: Choi H et al. Circ Cardiovasc Imaging. 2020 Sep;13(9):e011199.

Biologics used as treatment for psoriasis may also help reduce lipid-rich necrotic core (LRNC), a high-risk plaque associated with cardiovascular events, recent research from a prospective, observational study suggests.

Waldemarus/Thinkstock

Cardiac CT scans performed on patients with psoriasis 1 year after starting biologic therapy revealed a reduction in LRNC, compared with patients who were not receiving biologics, according to Harry Choi, MD, of the National Heart, Lung, and Blood Institute at the National Institutes of Health and colleagues. The association with reduction in LRNC and biologic therapy remained significant when adjusted for type of biologic. “These findings demonstrate that LRNC may be modulated by the control of systemic inflammation,” the researchers wrote in their study, published Sept. 15 in Circulation: Cardiovascular Imaging.

Dr. Choi and colleagues evaluated 289 patients with psoriasis within the Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative cohort. The patients had a mean age of 50 years and a mean body mass index of 29.4 kg/m², as well as a mean Psoriasis Area and Severity Index (PASI) score of 6.0. At baseline, 29% of patients had hypertension, 41% had hyperlipidemia, their mean Framingham risk score was 1.9, and a three-quarters (212 of 289) had mild to moderate psoriasis.

Changes in LRNC were observed at 1 year, compared with baseline prior to and after receiving biologic therapy (124 patients) in comparison with patients who did not undergo biologic therapy (85 patients). Biologic therapies were grouped by type, which included anti–tumor necrosis factor (anti-TNF), anti–interleukin (IL)–12/23, and anti–IL-17 biologics.

There were a significant associations between LRNC and Framingham risk score (standardized beta coefficient, 0.12; 95% confidence interval, 0.00-0.15; P = .045) and severity of psoriasis (beta, 0.13; 95% CI, 0.01-0.26; P = .029) at baseline.
 

Key findings

The researchers found a significant reduction in LRNC 1 year after patients began biologic therapy (median, 2.97 mm²; interquartile range, 1.99-4.66), compared with baseline (median, 3.12 mm²; IQR, 1.84-4.35) (P = .028), while patients who did not receive biologic therapy had nonsignificantly higher LRNC after 1 year (median, 3.12 mm²; IQR, 1.82-4.60), compared with baseline measurements (median, 3.34 mm²; IQR, 2.04–4.74) (P = .06).

The results remained significant after the researchers adjusted for psoriasis severity, Framingham risk score, BMI, use of statins (beta, −0.09; 95% CI, −0.01 to −0.18; P = .033). Significant reductions in LRNC also remained when analyzing patients receiving anti-TNF, anti–IL-12/23, and anti–IL-17 biologics independently, and there were no significant between-group differences in reduction of LRNC.
 

The potential of biologics for improving vascular health

Discussing the study results in a press release from the American Heart Association, senior author Nehal N. Mehta, MD, MSCE, FAHA, chief of the Lab of Inflammation and Cardiometabolic Diseases at the NHLBI at NIH, compared the effect biologic therapy had on coronary plaque reduction with that of statins.

“There is approximately 6%-8% reduction in coronary plaque following therapy with statins. Similarly, our treatment with biologic therapy reduced coronary plaque by the same amount after one year. These findings suggest that biologic therapy to treat psoriasis may be just as beneficial as statin therapy on heart arteries,” Dr. Mehta said in the release.

In an interview, Nieca Goldberg, MD, medical director of NYU Women’s Heart Program at NYU Langone Health, echoed Dr. Mehta’s commments and said psoriasis carries the “potential to treat two conditions with the same drug.”

“We know conditions such as psoriatic arthritis and rheumatoid arthritis cause chronic inflammation. Chronic inflammation causes injury to blood vessels and high-risk coronary plaque. Individuals with these inflammatory conditions are at high risk for heart attack,” she said. “This study shows that biologic treatment for psoriatic arthritis can reduce the presence of high-risk plaque. It shows the potential to treat chronic inflammation and high-risk coronary plaque.”

While the results show an association between use of biologics and LRNC reduction, the study design was observational and patients had a short follow-up period. Dr. Goldberg noted more studies are needed to evaluate the effect of biologics on reducing cardiovascular events such as a myocardial infarction.

“We have never before been able to show healing of an inflamed plaque like this in humans. Biologic therapy reduces systemic inflammation and immune activation, and it has a favorable impact on improving overall vascular health,” Dr. Mehta said in the press release. “Imagine if we can treat both psoriasis and coronary heart disease with one therapy – that is the question to be asked in future studies.”

This study was funded with support from the NHLBI Intramural Research Program and the NIH Medical Research Scholars Program at the National Institutes of Health. One investigator reports financial relationships with numerous pharmaceutical companies. The other authors report no relevant conflicts of interest. Dr. Mehta also reports numerous such relationships. Dr. Goldberg reports no relevant conflicts of interest.

SOURCE: Choi H et al. Circ Cardiovasc Imaging. 2020 Sep;13(9):e011199.

Bariatric surgery resolved nonalcoholic steatohepatitis (NASH) without worsening fibrosis in 84% of patients with evaluable biopsies, according to the findings of a prospective study.

The study included 180 severely or morbidly obese adults (body mass index >35 kg/m²) with NASH who underwent bariatric surgery at a center in France. Among 94 patients evaluated 5 years later, 68% had follow-up liver biopsies, of whom 84% (95% confidence interval, 73.1%-92.2%) met the primary endpoint of resolution of NASH without worsening of fibrosis. All histologic aspects of NASH had improved, median nonalcoholic fatty liver disease scores (NAS) fell from 5 (interquartile range, 4 to 5) to 1 (IQR, 0-2; P < .001), and 90% of patients achieved at least a 2-point NAS improvement. Hepatocellular ballooning also improved in 87.5% of patients. Baseline severity of NASH did not affect the chances of it resolving at 5 years. “The reduction of fibrosis [was] progressive, beginning during the first year and continuing through 5 years,” Guillaume Lassailly, MD, and associates wrote in Gastroenterology.

NASH is a priority for clinical research because of the substantial risk for subsequent cirrhosis, added Dr. Lassailly of CHU Lille (France). For NASH to resolve, most patients need to lose at least 7%-10% of their body weight, but “only 10% of patients reach this objective with lifestyle therapy at 1 year, and less than half maintain the weight loss 5 years later.” Despite ongoing drug development efforts, no medications have been approved for treating NASH. Although weight loss after bariatric surgery has been reported to resolve NASH in approximately 80% of patients at 1 year, longer-term data have been unavailable, and it has remained unclear whether bariatric surgery can slow or halt fibrosis progression.

All patients in this study had biopsy-confirmed NASH and at least a 5-year history of severe or morbid obesity as well as at least one comorbidity, such as diabetes mellitus or arterial hypertension. Patients were not heavy drinkers, and none had detectable markers of chronic liver disease.

Bariatric surgery produced a median 12-kg/m² drop in body mass index. At 5-year follow-up, 93% of patients meeting or exceeding this threshold who had biopsies performed showed resolution of NASH without worsening of fibrosis. Furthermore, 56% of patients (95% CI, 42.4%-69.3%) had no histologic evidence of fibrosis, including 45.5% of patients who had bridging fibrosis at baseline.

Participants in this study received intensive preoperative support, including evaluations by numerous specialists, a nutrition plan, and a 6- to 12-month therapeutic education program. Bariatric surgery techniques included Roux-en-Y gastric bypass, gastric banding, and sleeve gastrectomy. A subgroup analysis linked gastric bypass to a significantly higher probability of meeting the primary endpoint, compared with gastric banding. Refusal was the most common reason for not having a follow-up biopsy, the researchers said. “Patients without liver biopsy after bariatric surgery were not significantly different from those with a histological follow-up except for a lower BMI at 1 year. Baseline fibrosis did not influence the probability of undergoing histological reevaluation at 5 years.”

Two study participants died from surgical complications within 1 month after surgery, and one patient died from cardiac dysfunction 4 years later. No fatality was deemed liver related.

The study was funded by the French Ministry of Health, Conseil Régional Nord-Pas de Calais, National de la Recherche, and the European commission (FEDER). The researchers reported having no conflicts of interest.

SOURCE: Lassailly G et al. Gastroenterology. 2020 Jun 15. doi: 10.1053/j.gastro.2020.06.006.

Bariatric surgery resolved nonalcoholic steatohepatitis (NASH) without worsening fibrosis in 84% of patients with evaluable biopsies, according to the findings of a prospective study.

The study included 180 severely or morbidly obese adults (body mass index >35 kg/m²) with NASH who underwent bariatric surgery at a center in France. Among 94 patients evaluated 5 years later, 68% had follow-up liver biopsies, of whom 84% (95% confidence interval, 73.1%-92.2%) met the primary endpoint of resolution of NASH without worsening of fibrosis. All histologic aspects of NASH had improved, median nonalcoholic fatty liver disease scores (NAS) fell from 5 (interquartile range, 4 to 5) to 1 (IQR, 0-2; P < .001), and 90% of patients achieved at least a 2-point NAS improvement. Hepatocellular ballooning also improved in 87.5% of patients. Baseline severity of NASH did not affect the chances of it resolving at 5 years. “The reduction of fibrosis [was] progressive, beginning during the first year and continuing through 5 years,” Guillaume Lassailly, MD, and associates wrote in Gastroenterology.

NASH is a priority for clinical research because of the substantial risk for subsequent cirrhosis, added Dr. Lassailly of CHU Lille (France). For NASH to resolve, most patients need to lose at least 7%-10% of their body weight, but “only 10% of patients reach this objective with lifestyle therapy at 1 year, and less than half maintain the weight loss 5 years later.” Despite ongoing drug development efforts, no medications have been approved for treating NASH. Although weight loss after bariatric surgery has been reported to resolve NASH in approximately 80% of patients at 1 year, longer-term data have been unavailable, and it has remained unclear whether bariatric surgery can slow or halt fibrosis progression.

All patients in this study had biopsy-confirmed NASH and at least a 5-year history of severe or morbid obesity as well as at least one comorbidity, such as diabetes mellitus or arterial hypertension. Patients were not heavy drinkers, and none had detectable markers of chronic liver disease.

Bariatric surgery produced a median 12-kg/m² drop in body mass index. At 5-year follow-up, 93% of patients meeting or exceeding this threshold who had biopsies performed showed resolution of NASH without worsening of fibrosis. Furthermore, 56% of patients (95% CI, 42.4%-69.3%) had no histologic evidence of fibrosis, including 45.5% of patients who had bridging fibrosis at baseline.

Participants in this study received intensive preoperative support, including evaluations by numerous specialists, a nutrition plan, and a 6- to 12-month therapeutic education program. Bariatric surgery techniques included Roux-en-Y gastric bypass, gastric banding, and sleeve gastrectomy. A subgroup analysis linked gastric bypass to a significantly higher probability of meeting the primary endpoint, compared with gastric banding. Refusal was the most common reason for not having a follow-up biopsy, the researchers said. “Patients without liver biopsy after bariatric surgery were not significantly different from those with a histological follow-up except for a lower BMI at 1 year. Baseline fibrosis did not influence the probability of undergoing histological reevaluation at 5 years.”

Two study participants died from surgical complications within 1 month after surgery, and one patient died from cardiac dysfunction 4 years later. No fatality was deemed liver related.

The study was funded by the French Ministry of Health, Conseil Régional Nord-Pas de Calais, National de la Recherche, and the European commission (FEDER). The researchers reported having no conflicts of interest.

SOURCE: Lassailly G et al. Gastroenterology. 2020 Jun 15. doi: 10.1053/j.gastro.2020.06.006.

Bariatric surgery resolved nonalcoholic steatohepatitis (NASH) without worsening fibrosis in 84% of patients with evaluable biopsies, according to the findings of a prospective study.

The study included 180 severely or morbidly obese adults (body mass index >35 kg/m²) with NASH who underwent bariatric surgery at a center in France. Among 94 patients evaluated 5 years later, 68% had follow-up liver biopsies, of whom 84% (95% confidence interval, 73.1%-92.2%) met the primary endpoint of resolution of NASH without worsening of fibrosis. All histologic aspects of NASH had improved, median nonalcoholic fatty liver disease scores (NAS) fell from 5 (interquartile range, 4 to 5) to 1 (IQR, 0-2; P < .001), and 90% of patients achieved at least a 2-point NAS improvement. Hepatocellular ballooning also improved in 87.5% of patients. Baseline severity of NASH did not affect the chances of it resolving at 5 years. “The reduction of fibrosis [was] progressive, beginning during the first year and continuing through 5 years,” Guillaume Lassailly, MD, and associates wrote in Gastroenterology.

NASH is a priority for clinical research because of the substantial risk for subsequent cirrhosis, added Dr. Lassailly of CHU Lille (France). For NASH to resolve, most patients need to lose at least 7%-10% of their body weight, but “only 10% of patients reach this objective with lifestyle therapy at 1 year, and less than half maintain the weight loss 5 years later.” Despite ongoing drug development efforts, no medications have been approved for treating NASH. Although weight loss after bariatric surgery has been reported to resolve NASH in approximately 80% of patients at 1 year, longer-term data have been unavailable, and it has remained unclear whether bariatric surgery can slow or halt fibrosis progression.

All patients in this study had biopsy-confirmed NASH and at least a 5-year history of severe or morbid obesity as well as at least one comorbidity, such as diabetes mellitus or arterial hypertension. Patients were not heavy drinkers, and none had detectable markers of chronic liver disease.

Bariatric surgery produced a median 12-kg/m² drop in body mass index. At 5-year follow-up, 93% of patients meeting or exceeding this threshold who had biopsies performed showed resolution of NASH without worsening of fibrosis. Furthermore, 56% of patients (95% CI, 42.4%-69.3%) had no histologic evidence of fibrosis, including 45.5% of patients who had bridging fibrosis at baseline.

Participants in this study received intensive preoperative support, including evaluations by numerous specialists, a nutrition plan, and a 6- to 12-month therapeutic education program. Bariatric surgery techniques included Roux-en-Y gastric bypass, gastric banding, and sleeve gastrectomy. A subgroup analysis linked gastric bypass to a significantly higher probability of meeting the primary endpoint, compared with gastric banding. Refusal was the most common reason for not having a follow-up biopsy, the researchers said. “Patients without liver biopsy after bariatric surgery were not significantly different from those with a histological follow-up except for a lower BMI at 1 year. Baseline fibrosis did not influence the probability of undergoing histological reevaluation at 5 years.”

Two study participants died from surgical complications within 1 month after surgery, and one patient died from cardiac dysfunction 4 years later. No fatality was deemed liver related.

The study was funded by the French Ministry of Health, Conseil Régional Nord-Pas de Calais, National de la Recherche, and the European commission (FEDER). The researchers reported having no conflicts of interest.

SOURCE: Lassailly G et al. Gastroenterology. 2020 Jun 15. doi: 10.1053/j.gastro.2020.06.006.

Amarin’s hopes of fending off generic competition for its blockbuster high-strength eicosapentaenoic acid product, icosapent ethyl (Vascepa), have dimmed following a decision by the U.S. Court of Appeals for the Federal Circuit in the company’s ongoing patent litigation.

The court upheld the March ruling by the District Court for the District of Nevada in favor of two generic companies in connection with their abbreviated new drug applications (ANDAs) for the product.

Amarin said it is currently reviewing its legal options and within 30 days expects to file a petition for an en banc review of the current decision by the full panel of 12 active judges at the Court of Appeals for the Federal Circuit.

“We are extremely disappointed with [the] ruling and plan to vigorously pursue available remedies,” John Thero, Amarin president and chief executive officer, said in a statement.

In 2012, Vascepa became the first and only prescription treatment approved by the Food and Drug Administration made up solely of the active ingredient icosapent ethyl, a unique form of eicosapentaenoic acid. It was initially approved for the reduction of very high triglyceride levels (≥500 mg/dL).

In late 2019, the FDA extended the indication to reduce the risk for cardiovascular events in people with elevated triglyceride levels and either established CV disease or diabetes with other CV risk factors.

The extended indication was based on results of the landmark REDUCE-IT trial, which showed a 25% relative risk reduction in major adverse CV events with icosapent ethyl, compared with placebo, in patients with triglyceride levels above 135 mg/dL and who had CV disease (70% of the study population), or who were high-risk primary-prevention patients with diabetes and one additional risk factor (30% of the study population).

According to Amarin, since its launch, Vascepa has been prescribed more than 8 million times.

The company said demand for the product in the United States remains “strong” and indicated that, despite the legal setback, it would continue promotional efforts. The company is also seeking additional regulatory approvals in China, Europe, and additional countries in the Middle East.

“We are particularly excited about the anticipated commercialization opportunities for Vascepa in Europe as we prepare for expected approval and launch in early 2021,” Mr. Thero said.

The company anticipates 10 years of market protection because of regulatory exclusivity in the European Union once approved, and said patent protection could extend into 2039.

Only Vascepa sold in the United States is subject to this litigation and judgment. No generic litigation is pending outside the United States, Amarin said.

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

Amarin’s hopes of fending off generic competition for its blockbuster high-strength eicosapentaenoic acid product, icosapent ethyl (Vascepa), have dimmed following a decision by the U.S. Court of Appeals for the Federal Circuit in the company’s ongoing patent litigation.

The court upheld the March ruling by the District Court for the District of Nevada in favor of two generic companies in connection with their abbreviated new drug applications (ANDAs) for the product.

Amarin said it is currently reviewing its legal options and within 30 days expects to file a petition for an en banc review of the current decision by the full panel of 12 active judges at the Court of Appeals for the Federal Circuit.

“We are extremely disappointed with [the] ruling and plan to vigorously pursue available remedies,” John Thero, Amarin president and chief executive officer, said in a statement.

In 2012, Vascepa became the first and only prescription treatment approved by the Food and Drug Administration made up solely of the active ingredient icosapent ethyl, a unique form of eicosapentaenoic acid. It was initially approved for the reduction of very high triglyceride levels (≥500 mg/dL).

In late 2019, the FDA extended the indication to reduce the risk for cardiovascular events in people with elevated triglyceride levels and either established CV disease or diabetes with other CV risk factors.

The extended indication was based on results of the landmark REDUCE-IT trial, which showed a 25% relative risk reduction in major adverse CV events with icosapent ethyl, compared with placebo, in patients with triglyceride levels above 135 mg/dL and who had CV disease (70% of the study population), or who were high-risk primary-prevention patients with diabetes and one additional risk factor (30% of the study population).

According to Amarin, since its launch, Vascepa has been prescribed more than 8 million times.

The company said demand for the product in the United States remains “strong” and indicated that, despite the legal setback, it would continue promotional efforts. The company is also seeking additional regulatory approvals in China, Europe, and additional countries in the Middle East.

“We are particularly excited about the anticipated commercialization opportunities for Vascepa in Europe as we prepare for expected approval and launch in early 2021,” Mr. Thero said.

The company anticipates 10 years of market protection because of regulatory exclusivity in the European Union once approved, and said patent protection could extend into 2039.

Only Vascepa sold in the United States is subject to this litigation and judgment. No generic litigation is pending outside the United States, Amarin said.

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

Amarin’s hopes of fending off generic competition for its blockbuster high-strength eicosapentaenoic acid product, icosapent ethyl (Vascepa), have dimmed following a decision by the U.S. Court of Appeals for the Federal Circuit in the company’s ongoing patent litigation.

The court upheld the March ruling by the District Court for the District of Nevada in favor of two generic companies in connection with their abbreviated new drug applications (ANDAs) for the product.

Amarin said it is currently reviewing its legal options and within 30 days expects to file a petition for an en banc review of the current decision by the full panel of 12 active judges at the Court of Appeals for the Federal Circuit.

“We are extremely disappointed with [the] ruling and plan to vigorously pursue available remedies,” John Thero, Amarin president and chief executive officer, said in a statement.

In 2012, Vascepa became the first and only prescription treatment approved by the Food and Drug Administration made up solely of the active ingredient icosapent ethyl, a unique form of eicosapentaenoic acid. It was initially approved for the reduction of very high triglyceride levels (≥500 mg/dL).

In late 2019, the FDA extended the indication to reduce the risk for cardiovascular events in people with elevated triglyceride levels and either established CV disease or diabetes with other CV risk factors.

The extended indication was based on results of the landmark REDUCE-IT trial, which showed a 25% relative risk reduction in major adverse CV events with icosapent ethyl, compared with placebo, in patients with triglyceride levels above 135 mg/dL and who had CV disease (70% of the study population), or who were high-risk primary-prevention patients with diabetes and one additional risk factor (30% of the study population).

According to Amarin, since its launch, Vascepa has been prescribed more than 8 million times.

The company said demand for the product in the United States remains “strong” and indicated that, despite the legal setback, it would continue promotional efforts. The company is also seeking additional regulatory approvals in China, Europe, and additional countries in the Middle East.

“We are particularly excited about the anticipated commercialization opportunities for Vascepa in Europe as we prepare for expected approval and launch in early 2021,” Mr. Thero said.

The company anticipates 10 years of market protection because of regulatory exclusivity in the European Union once approved, and said patent protection could extend into 2039.

Only Vascepa sold in the United States is subject to this litigation and judgment. No generic litigation is pending outside the United States, Amarin said.

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

Final 18-month results of the EVAPORATE trial suggest icosapent ethyl (Vascepa) provides even greater slowing of coronary plaque progression when added to statins for patients with high triglyceride levels, but not all cardiologists are convinced.

The study was designed to explore a potential mechanism behind the cardiovascular event reduction in REDUCE-IT. Previously reported interim results showed that, after 9 months, the pharmaceutical-grade omega-3 fatty acid formation significantly slowed the progression of several plaque types but not the primary endpoint of change in low-attenuation plaque volume on multidetector CT.

From baseline to 18-month follow-up, however, the primary endpoint was significantly reduced by 17% in the icosapent ethyl group, whereas low-attenuation plaque volumes increased by 109% in the placebo group (P = .0061).

Significant declines were also seen with icosapent ethyl 4 g/day versus the mineral oil placebo for all other plaque types except dense calcium after adjustment for age, sex, diabetes, hypertension, and triglyceride levels at baseline:

• Dense calcium: –1% versus 15% (P = .0531).
• Fibro-fatty: –34% versus 32% (P = .0002).
• Fibrous: –20% versus 1% (P = .0028).
• Noncalcified: –19% versus 9% (P = .0005).
• Total plaque: –9% versus 11% (P = .0019).

The results parallel nicely with recent clinical data from REDUCE-IT REVASC, in which icosapent ethyl 4 g/day provided a very early benefit on first revascularization events that reached statistical significance after only 11 months (hazard ratio, 0.66), principal investigator Matthew Budoff, MD, director of cardiac CT at Harbor–University of California, Los Angeles, Medical Center in Torrance, Calif., said during the virtual European Society of Cardiology Congress 2020.

The findings were also published simultaneously in the European Heart Journal and quickly prompted a flurry of comments on social media.

Some were supportive. Christopher Cannon, MD, of Harvard Medical School, Boston; Dan Soffer, MD, a lipidologist at the University of Pennsylvania, Philadelphia; and Viet Le, MPAS, PA, a researcher at the Intermountain Heart Institute, Murray, Utah, took to Twitter to praise Dr. Budoff and the final results of the mechanistic study. Dr. Soffer called the study “elegant,” while Dr. Cannon said the results provide “important mechanistic data on plaque character.”

Others were highly critical, including a poll questioning whether the article should be retracted or revised.

Ibrahim H. Tanboga, MD, PhD, a cardiology professor and biostatistician at Hisar Intercontinental Hospital in Istanbul, questioned how the longitudinal change in low-attenuation plaque was possible clinically; his plot of the data showed these lesions getting worse in both arms before getting better in both arms.

A more volatile exchange concerned whether there were differences in the baseline characteristics between the two groups and whether the data might have been unblinded.

“I am sympathetic to the boss of a big laboratory [who] might not know how every step of the process was done and therefore might not be aware of opportunities for accidental bias. This can easily happen in a large and active department,” Darrel Francis, MD, professor of cardiology at the National Heart and Lung Institute, Imperial College, London, said in an interview.

An alternative explanation proffered on Twitter was that the interim analysis found no significant differences in baseline measures because it used nonparametric tests, whereas log transformation was applied to the final data. In any event, the tweets prompted a sharp rebuke from Dr. Budoff.

Dr. Francis raised another point of contention on Twitter regarding the degree of plaque progression in the placebo group.

In an interview, Dr. Francis pointed out that the final data represent the percentage change in the logarithm, not the actual percentage change in atheroma. So the increase in total atheroma volume in the placebo arm is not 11% but rather a scaling-up by 100.4 or 2.51, in other words, 151%.

He also offered a “less subtle feature of possible erroneous data,” in that the abstract reported low-attenuation plaque “more than doubles” in 18 months, which he described as a “ghastly supercharged version of Moore’s law for atheroma, instead of microchips.”

So “either it’s a mistake in the measurement or the placebo is harmful, because I can’t see how this is sustainable,” he said. “Why isn’t everyone dead from coronary disease?”

Concerns were raised previously over the possibility that the mineral oil placebo used in both EVAPORATE and REDUCE-IT could be having ill effects, notably, by increasing LDL cholesterol and C-reactive protein levels.

In an interview, Steven Nissen, MD, who is chair of cardiovascular medicine at the Cleveland Clinic and has been among the critics of the mineral oil placebo, also questioned the plaque progression over the 18 months.

“I’ve published more than dozen regression/progression trials, and we have never seen anything like this in a placebo group, ever,” he said. “If this was a clean placebo, why would this happen in a short amount of time?

“I’m concerned this is all about an increase, in the case of REDUCE-IT, in morbidity and mortality in the placebo group, and in the EVAPORATE trial, an increase in plaque in the placebo group,” Dr. Nissen said. “So this raises serious doubts about whether there is any benefit to icosapent ethyl.”

Asked about the 109% increase, Dr. Budoff said in an interview that low-attenuation plaque represents a much smaller quantity of overall plaque volume. “So the percentages might be exaggerated if you look at just percentage change because they;re small volumes.”

He also noted that previous trials that evaluated atherosclerosis progression used intravascular ultrasound (IVUS), whereas EVAPORATE is the first to make the transition to CT angiography-based analysis of plaque progression.

“I would point out that Dr. Nissen has only worked on intravascular ultrasound, which, while it’s parallel in its ability to measure plaque, measures different volumes and measures it in a totally different way,” said Dr. Budoff. “So I don’t think we can directly compare the results of CT angiography to Dr. Nissen’s examples of IVUS.”

During his presentation, Dr. Budoff highlighted their recent data showing a similar rate of plaque progression between the mineral oil placebo in EVAPORATE and a cellulose-based placebo in the Garlic5 study. “So we have high confidence that the benefits seen in this trial with icosapent ethyl represent icosapent ethyl’s beneficial effects on atherosclerosis and not harm of mineral oil,” he said.

Exactly how icosapent ethyl is slowing atherosclerosis, however, is not fully known, Dr. Budoff said in an interview. “It might be inflammation and oxidation; those have both been shown to be better with icosapent ethyl, but I don’t think we fully understand the implications of these results.”

Dr. Budoff dismissed tweets that suggest the data might have been unblinded as unprofessional and said they are requesting that Imperial College have Francis cease and desist.

“He doesn’t have the actual data, so there is no way to do statistics without the dataset. The whole thing is inappropriate,” Dr. Budoff said.

Amarin Pharma provided funding and drug for the trial. Dr. Budoff has received research funding from and has served as a speaker for Amarin Pharma, Amgen, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Pfizer and has served as a speaker for Bristol-Myers Squibb. Dr. Francis has disclosed no relevant financial relationships..

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

Final 18-month results of the EVAPORATE trial suggest icosapent ethyl (Vascepa) provides even greater slowing of coronary plaque progression when added to statins for patients with high triglyceride levels, but not all cardiologists are convinced.

The study was designed to explore a potential mechanism behind the cardiovascular event reduction in REDUCE-IT. Previously reported interim results showed that, after 9 months, the pharmaceutical-grade omega-3 fatty acid formation significantly slowed the progression of several plaque types but not the primary endpoint of change in low-attenuation plaque volume on multidetector CT.

From baseline to 18-month follow-up, however, the primary endpoint was significantly reduced by 17% in the icosapent ethyl group, whereas low-attenuation plaque volumes increased by 109% in the placebo group (P = .0061).

Significant declines were also seen with icosapent ethyl 4 g/day versus the mineral oil placebo for all other plaque types except dense calcium after adjustment for age, sex, diabetes, hypertension, and triglyceride levels at baseline:

• Dense calcium: –1% versus 15% (P = .0531).
• Fibro-fatty: –34% versus 32% (P = .0002).
• Fibrous: –20% versus 1% (P = .0028).
• Noncalcified: –19% versus 9% (P = .0005).
• Total plaque: –9% versus 11% (P = .0019).

The results parallel nicely with recent clinical data from REDUCE-IT REVASC, in which icosapent ethyl 4 g/day provided a very early benefit on first revascularization events that reached statistical significance after only 11 months (hazard ratio, 0.66), principal investigator Matthew Budoff, MD, director of cardiac CT at Harbor–University of California, Los Angeles, Medical Center in Torrance, Calif., said during the virtual European Society of Cardiology Congress 2020.

The findings were also published simultaneously in the European Heart Journal and quickly prompted a flurry of comments on social media.

Some were supportive. Christopher Cannon, MD, of Harvard Medical School, Boston; Dan Soffer, MD, a lipidologist at the University of Pennsylvania, Philadelphia; and Viet Le, MPAS, PA, a researcher at the Intermountain Heart Institute, Murray, Utah, took to Twitter to praise Dr. Budoff and the final results of the mechanistic study. Dr. Soffer called the study “elegant,” while Dr. Cannon said the results provide “important mechanistic data on plaque character.”

Others were highly critical, including a poll questioning whether the article should be retracted or revised.

Ibrahim H. Tanboga, MD, PhD, a cardiology professor and biostatistician at Hisar Intercontinental Hospital in Istanbul, questioned how the longitudinal change in low-attenuation plaque was possible clinically; his plot of the data showed these lesions getting worse in both arms before getting better in both arms.

A more volatile exchange concerned whether there were differences in the baseline characteristics between the two groups and whether the data might have been unblinded.

“I am sympathetic to the boss of a big laboratory [who] might not know how every step of the process was done and therefore might not be aware of opportunities for accidental bias. This can easily happen in a large and active department,” Darrel Francis, MD, professor of cardiology at the National Heart and Lung Institute, Imperial College, London, said in an interview.

An alternative explanation proffered on Twitter was that the interim analysis found no significant differences in baseline measures because it used nonparametric tests, whereas log transformation was applied to the final data. In any event, the tweets prompted a sharp rebuke from Dr. Budoff.

Dr. Francis raised another point of contention on Twitter regarding the degree of plaque progression in the placebo group.

In an interview, Dr. Francis pointed out that the final data represent the percentage change in the logarithm, not the actual percentage change in atheroma. So the increase in total atheroma volume in the placebo arm is not 11% but rather a scaling-up by 100.4 or 2.51, in other words, 151%.

He also offered a “less subtle feature of possible erroneous data,” in that the abstract reported low-attenuation plaque “more than doubles” in 18 months, which he described as a “ghastly supercharged version of Moore’s law for atheroma, instead of microchips.”

So “either it’s a mistake in the measurement or the placebo is harmful, because I can’t see how this is sustainable,” he said. “Why isn’t everyone dead from coronary disease?”

Concerns were raised previously over the possibility that the mineral oil placebo used in both EVAPORATE and REDUCE-IT could be having ill effects, notably, by increasing LDL cholesterol and C-reactive protein levels.

In an interview, Steven Nissen, MD, who is chair of cardiovascular medicine at the Cleveland Clinic and has been among the critics of the mineral oil placebo, also questioned the plaque progression over the 18 months.

“I’ve published more than dozen regression/progression trials, and we have never seen anything like this in a placebo group, ever,” he said. “If this was a clean placebo, why would this happen in a short amount of time?

“I’m concerned this is all about an increase, in the case of REDUCE-IT, in morbidity and mortality in the placebo group, and in the EVAPORATE trial, an increase in plaque in the placebo group,” Dr. Nissen said. “So this raises serious doubts about whether there is any benefit to icosapent ethyl.”

Asked about the 109% increase, Dr. Budoff said in an interview that low-attenuation plaque represents a much smaller quantity of overall plaque volume. “So the percentages might be exaggerated if you look at just percentage change because they;re small volumes.”

He also noted that previous trials that evaluated atherosclerosis progression used intravascular ultrasound (IVUS), whereas EVAPORATE is the first to make the transition to CT angiography-based analysis of plaque progression.

“I would point out that Dr. Nissen has only worked on intravascular ultrasound, which, while it’s parallel in its ability to measure plaque, measures different volumes and measures it in a totally different way,” said Dr. Budoff. “So I don’t think we can directly compare the results of CT angiography to Dr. Nissen’s examples of IVUS.”

During his presentation, Dr. Budoff highlighted their recent data showing a similar rate of plaque progression between the mineral oil placebo in EVAPORATE and a cellulose-based placebo in the Garlic5 study. “So we have high confidence that the benefits seen in this trial with icosapent ethyl represent icosapent ethyl’s beneficial effects on atherosclerosis and not harm of mineral oil,” he said.

Exactly how icosapent ethyl is slowing atherosclerosis, however, is not fully known, Dr. Budoff said in an interview. “It might be inflammation and oxidation; those have both been shown to be better with icosapent ethyl, but I don’t think we fully understand the implications of these results.”

Dr. Budoff dismissed tweets that suggest the data might have been unblinded as unprofessional and said they are requesting that Imperial College have Francis cease and desist.

“He doesn’t have the actual data, so there is no way to do statistics without the dataset. The whole thing is inappropriate,” Dr. Budoff said.

Amarin Pharma provided funding and drug for the trial. Dr. Budoff has received research funding from and has served as a speaker for Amarin Pharma, Amgen, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Pfizer and has served as a speaker for Bristol-Myers Squibb. Dr. Francis has disclosed no relevant financial relationships..

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

Final 18-month results of the EVAPORATE trial suggest icosapent ethyl (Vascepa) provides even greater slowing of coronary plaque progression when added to statins for patients with high triglyceride levels, but not all cardiologists are convinced.

The study was designed to explore a potential mechanism behind the cardiovascular event reduction in REDUCE-IT. Previously reported interim results showed that, after 9 months, the pharmaceutical-grade omega-3 fatty acid formation significantly slowed the progression of several plaque types but not the primary endpoint of change in low-attenuation plaque volume on multidetector CT.

From baseline to 18-month follow-up, however, the primary endpoint was significantly reduced by 17% in the icosapent ethyl group, whereas low-attenuation plaque volumes increased by 109% in the placebo group (P = .0061).

Significant declines were also seen with icosapent ethyl 4 g/day versus the mineral oil placebo for all other plaque types except dense calcium after adjustment for age, sex, diabetes, hypertension, and triglyceride levels at baseline:

• Dense calcium: –1% versus 15% (P = .0531).
• Fibro-fatty: –34% versus 32% (P = .0002).
• Fibrous: –20% versus 1% (P = .0028).
• Noncalcified: –19% versus 9% (P = .0005).
• Total plaque: –9% versus 11% (P = .0019).

The results parallel nicely with recent clinical data from REDUCE-IT REVASC, in which icosapent ethyl 4 g/day provided a very early benefit on first revascularization events that reached statistical significance after only 11 months (hazard ratio, 0.66), principal investigator Matthew Budoff, MD, director of cardiac CT at Harbor–University of California, Los Angeles, Medical Center in Torrance, Calif., said during the virtual European Society of Cardiology Congress 2020.

The findings were also published simultaneously in the European Heart Journal and quickly prompted a flurry of comments on social media.

Some were supportive. Christopher Cannon, MD, of Harvard Medical School, Boston; Dan Soffer, MD, a lipidologist at the University of Pennsylvania, Philadelphia; and Viet Le, MPAS, PA, a researcher at the Intermountain Heart Institute, Murray, Utah, took to Twitter to praise Dr. Budoff and the final results of the mechanistic study. Dr. Soffer called the study “elegant,” while Dr. Cannon said the results provide “important mechanistic data on plaque character.”

Others were highly critical, including a poll questioning whether the article should be retracted or revised.

Ibrahim H. Tanboga, MD, PhD, a cardiology professor and biostatistician at Hisar Intercontinental Hospital in Istanbul, questioned how the longitudinal change in low-attenuation plaque was possible clinically; his plot of the data showed these lesions getting worse in both arms before getting better in both arms.

A more volatile exchange concerned whether there were differences in the baseline characteristics between the two groups and whether the data might have been unblinded.

“I am sympathetic to the boss of a big laboratory [who] might not know how every step of the process was done and therefore might not be aware of opportunities for accidental bias. This can easily happen in a large and active department,” Darrel Francis, MD, professor of cardiology at the National Heart and Lung Institute, Imperial College, London, said in an interview.

An alternative explanation proffered on Twitter was that the interim analysis found no significant differences in baseline measures because it used nonparametric tests, whereas log transformation was applied to the final data. In any event, the tweets prompted a sharp rebuke from Dr. Budoff.

Dr. Francis raised another point of contention on Twitter regarding the degree of plaque progression in the placebo group.

In an interview, Dr. Francis pointed out that the final data represent the percentage change in the logarithm, not the actual percentage change in atheroma. So the increase in total atheroma volume in the placebo arm is not 11% but rather a scaling-up by 100.4 or 2.51, in other words, 151%.

He also offered a “less subtle feature of possible erroneous data,” in that the abstract reported low-attenuation plaque “more than doubles” in 18 months, which he described as a “ghastly supercharged version of Moore’s law for atheroma, instead of microchips.”

So “either it’s a mistake in the measurement or the placebo is harmful, because I can’t see how this is sustainable,” he said. “Why isn’t everyone dead from coronary disease?”

Concerns were raised previously over the possibility that the mineral oil placebo used in both EVAPORATE and REDUCE-IT could be having ill effects, notably, by increasing LDL cholesterol and C-reactive protein levels.

In an interview, Steven Nissen, MD, who is chair of cardiovascular medicine at the Cleveland Clinic and has been among the critics of the mineral oil placebo, also questioned the plaque progression over the 18 months.

“I’ve published more than dozen regression/progression trials, and we have never seen anything like this in a placebo group, ever,” he said. “If this was a clean placebo, why would this happen in a short amount of time?

“I’m concerned this is all about an increase, in the case of REDUCE-IT, in morbidity and mortality in the placebo group, and in the EVAPORATE trial, an increase in plaque in the placebo group,” Dr. Nissen said. “So this raises serious doubts about whether there is any benefit to icosapent ethyl.”

Asked about the 109% increase, Dr. Budoff said in an interview that low-attenuation plaque represents a much smaller quantity of overall plaque volume. “So the percentages might be exaggerated if you look at just percentage change because they;re small volumes.”

He also noted that previous trials that evaluated atherosclerosis progression used intravascular ultrasound (IVUS), whereas EVAPORATE is the first to make the transition to CT angiography-based analysis of plaque progression.

“I would point out that Dr. Nissen has only worked on intravascular ultrasound, which, while it’s parallel in its ability to measure plaque, measures different volumes and measures it in a totally different way,” said Dr. Budoff. “So I don’t think we can directly compare the results of CT angiography to Dr. Nissen’s examples of IVUS.”

During his presentation, Dr. Budoff highlighted their recent data showing a similar rate of plaque progression between the mineral oil placebo in EVAPORATE and a cellulose-based placebo in the Garlic5 study. “So we have high confidence that the benefits seen in this trial with icosapent ethyl represent icosapent ethyl’s beneficial effects on atherosclerosis and not harm of mineral oil,” he said.

Exactly how icosapent ethyl is slowing atherosclerosis, however, is not fully known, Dr. Budoff said in an interview. “It might be inflammation and oxidation; those have both been shown to be better with icosapent ethyl, but I don’t think we fully understand the implications of these results.”

Dr. Budoff dismissed tweets that suggest the data might have been unblinded as unprofessional and said they are requesting that Imperial College have Francis cease and desist.

“He doesn’t have the actual data, so there is no way to do statistics without the dataset. The whole thing is inappropriate,” Dr. Budoff said.

Amarin Pharma provided funding and drug for the trial. Dr. Budoff has received research funding from and has served as a speaker for Amarin Pharma, Amgen, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Pfizer and has served as a speaker for Bristol-Myers Squibb. Dr. Francis has disclosed no relevant financial relationships..

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

Early administration of evolocumab significantly reduced levels of LDL cholesterol in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention, according to data from an open-label randomized trial of 102 adults in Japan.

Data from previous studies have shown that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can reduce LDL cholesterol in acute coronary syndrome patients, wrote Tomoaki Okada, MD, of Kagawa (Japan) Prefectural Central Hospital and colleagues.

In particular, “The EVOPACS trial [J Am Coll Cardiol 2019; 74:2452-62] reported that evolocumab therapy initiated at an early phase of ACS showed [LDL cholesterol] level reduction by 4-8 weeks,” they said.

“However, the 4-week efficacy of PCSK9 inhibitor therapy combined with a statin remains unknown,” they said.

In a study presented at the virtual annual congress of the European Society of Cardiology and published simultaneously in JACC: Cardiovascular Interventions, the researchers randomized 52 patients to receive 140 mg of evolocumab subcutaneously within 24 hours of indexed percutaneous coronary intervention and again after 2 weeks. A group of 50 controls received evolocumab after PCI only, but no additional dose after 2 weeks.

The average age of the patients was 65 years, 88% were men, and 26% had a history of statin treatment.

A total of 49 patients in each group were included in the final analysis, with a primary outcome of change in LDL cholesterol levels from baseline to 4 weeks.

Baseline LCL cholesterol levels were 120.8 mg/dL and 124.7 mg/dL in the evolocumab and control groups, respectively. Changes from baseline were significantly greater in the evolocumab group, compared with controls, at –76% and –33%, respectively.

All patients in the evolocumab group and 27% of patients in the control groups achieved LDL cholesterol levels of less than 70 mg/dL at 4 weeks. In addition, 92% and 96% of evolocumab patients achieved LDL cholesterol levels less than 55 mg/dL at 2 weeks and 4 weeks, respectively.

Overall changes in non-HDL cholesterol, HDL cholesterol, and small dense LDL in the evolocumab and control groups were –66.2% and –26.0%; 2.8% and –0.7%; and –67% and –13.8%, respectively. Of these, changes in non-HDL cholesterol and small dense LDL were significantly different between the groups.

In addition, patients in the evolocumab group showed a 3% decrease in lipoprotein, compared with an 82% increase in the control group. This finding suggests the additional benefit of including evolocumab for managing residual risk in patients with high lipoprotein(a) levels” after acute MI, the researchers noted.

Adverse events and serious adverse events were similar between the groups.

‘Early and strong’ LDL cholesterol lowering best for preventing repeat events

“By using the PCSK9 inhibitors, we have the opportunity to lower LDL cholesterol [LDL-C]” both quickly and dramatically, said Heinz Drexel, MD, in an interview.

“This Japanese study shows that very low LDL-C levels can be obtained as fast as within 4 weeks,” he said. “This fits into the concept that risk for future infarctions and strokes is best reduced by early and strong LDL-C lowering,” he explained.

Dr. Drexel said that he was not surprised by the magnitude of the decrease in LDL cholesterol in study findings in light of the EVOPACS study and other research, as well as his own clinical experience.

“The primary message for doctors is that it is now possible to achieve these low levels of LDL-C in a short time,” he said.

“Additional research must prove that this low LDL-C translates to reduction of MIs and strokes, and there is increasing evidence that this will happen,” Dr. Drexel noted.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Drexel had no financial conflicts to disclose.

SOURCE: Okada T et al. ESC 2020. JACC Cardiovascular Interventions. 2020 Aug 28. doi: 10.1016/j.jcin.2020.08.026.

Early administration of evolocumab significantly reduced levels of LDL cholesterol in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention, according to data from an open-label randomized trial of 102 adults in Japan.

Data from previous studies have shown that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can reduce LDL cholesterol in acute coronary syndrome patients, wrote Tomoaki Okada, MD, of Kagawa (Japan) Prefectural Central Hospital and colleagues.

In particular, “The EVOPACS trial [J Am Coll Cardiol 2019; 74:2452-62] reported that evolocumab therapy initiated at an early phase of ACS showed [LDL cholesterol] level reduction by 4-8 weeks,” they said.

“However, the 4-week efficacy of PCSK9 inhibitor therapy combined with a statin remains unknown,” they said.

In a study presented at the virtual annual congress of the European Society of Cardiology and published simultaneously in JACC: Cardiovascular Interventions, the researchers randomized 52 patients to receive 140 mg of evolocumab subcutaneously within 24 hours of indexed percutaneous coronary intervention and again after 2 weeks. A group of 50 controls received evolocumab after PCI only, but no additional dose after 2 weeks.

The average age of the patients was 65 years, 88% were men, and 26% had a history of statin treatment.

A total of 49 patients in each group were included in the final analysis, with a primary outcome of change in LDL cholesterol levels from baseline to 4 weeks.

Baseline LCL cholesterol levels were 120.8 mg/dL and 124.7 mg/dL in the evolocumab and control groups, respectively. Changes from baseline were significantly greater in the evolocumab group, compared with controls, at –76% and –33%, respectively.

All patients in the evolocumab group and 27% of patients in the control groups achieved LDL cholesterol levels of less than 70 mg/dL at 4 weeks. In addition, 92% and 96% of evolocumab patients achieved LDL cholesterol levels less than 55 mg/dL at 2 weeks and 4 weeks, respectively.

Overall changes in non-HDL cholesterol, HDL cholesterol, and small dense LDL in the evolocumab and control groups were –66.2% and –26.0%; 2.8% and –0.7%; and –67% and –13.8%, respectively. Of these, changes in non-HDL cholesterol and small dense LDL were significantly different between the groups.

In addition, patients in the evolocumab group showed a 3% decrease in lipoprotein, compared with an 82% increase in the control group. This finding suggests the additional benefit of including evolocumab for managing residual risk in patients with high lipoprotein(a) levels” after acute MI, the researchers noted.

Adverse events and serious adverse events were similar between the groups.

‘Early and strong’ LDL cholesterol lowering best for preventing repeat events

“By using the PCSK9 inhibitors, we have the opportunity to lower LDL cholesterol [LDL-C]” both quickly and dramatically, said Heinz Drexel, MD, in an interview.

“This Japanese study shows that very low LDL-C levels can be obtained as fast as within 4 weeks,” he said. “This fits into the concept that risk for future infarctions and strokes is best reduced by early and strong LDL-C lowering,” he explained.

Dr. Drexel said that he was not surprised by the magnitude of the decrease in LDL cholesterol in study findings in light of the EVOPACS study and other research, as well as his own clinical experience.

“The primary message for doctors is that it is now possible to achieve these low levels of LDL-C in a short time,” he said.

“Additional research must prove that this low LDL-C translates to reduction of MIs and strokes, and there is increasing evidence that this will happen,” Dr. Drexel noted.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Drexel had no financial conflicts to disclose.

SOURCE: Okada T et al. ESC 2020. JACC Cardiovascular Interventions. 2020 Aug 28. doi: 10.1016/j.jcin.2020.08.026.

Early administration of evolocumab significantly reduced levels of LDL cholesterol in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention, according to data from an open-label randomized trial of 102 adults in Japan.

Data from previous studies have shown that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can reduce LDL cholesterol in acute coronary syndrome patients, wrote Tomoaki Okada, MD, of Kagawa (Japan) Prefectural Central Hospital and colleagues.

In particular, “The EVOPACS trial [J Am Coll Cardiol 2019; 74:2452-62] reported that evolocumab therapy initiated at an early phase of ACS showed [LDL cholesterol] level reduction by 4-8 weeks,” they said.

“However, the 4-week efficacy of PCSK9 inhibitor therapy combined with a statin remains unknown,” they said.

In a study presented at the virtual annual congress of the European Society of Cardiology and published simultaneously in JACC: Cardiovascular Interventions, the researchers randomized 52 patients to receive 140 mg of evolocumab subcutaneously within 24 hours of indexed percutaneous coronary intervention and again after 2 weeks. A group of 50 controls received evolocumab after PCI only, but no additional dose after 2 weeks.

The average age of the patients was 65 years, 88% were men, and 26% had a history of statin treatment.

A total of 49 patients in each group were included in the final analysis, with a primary outcome of change in LDL cholesterol levels from baseline to 4 weeks.

Baseline LCL cholesterol levels were 120.8 mg/dL and 124.7 mg/dL in the evolocumab and control groups, respectively. Changes from baseline were significantly greater in the evolocumab group, compared with controls, at –76% and –33%, respectively.

All patients in the evolocumab group and 27% of patients in the control groups achieved LDL cholesterol levels of less than 70 mg/dL at 4 weeks. In addition, 92% and 96% of evolocumab patients achieved LDL cholesterol levels less than 55 mg/dL at 2 weeks and 4 weeks, respectively.

Overall changes in non-HDL cholesterol, HDL cholesterol, and small dense LDL in the evolocumab and control groups were –66.2% and –26.0%; 2.8% and –0.7%; and –67% and –13.8%, respectively. Of these, changes in non-HDL cholesterol and small dense LDL were significantly different between the groups.

In addition, patients in the evolocumab group showed a 3% decrease in lipoprotein, compared with an 82% increase in the control group. This finding suggests the additional benefit of including evolocumab for managing residual risk in patients with high lipoprotein(a) levels” after acute MI, the researchers noted.

Adverse events and serious adverse events were similar between the groups.

‘Early and strong’ LDL cholesterol lowering best for preventing repeat events

“By using the PCSK9 inhibitors, we have the opportunity to lower LDL cholesterol [LDL-C]” both quickly and dramatically, said Heinz Drexel, MD, in an interview.

“This Japanese study shows that very low LDL-C levels can be obtained as fast as within 4 weeks,” he said. “This fits into the concept that risk for future infarctions and strokes is best reduced by early and strong LDL-C lowering,” he explained.

Dr. Drexel said that he was not surprised by the magnitude of the decrease in LDL cholesterol in study findings in light of the EVOPACS study and other research, as well as his own clinical experience.

“The primary message for doctors is that it is now possible to achieve these low levels of LDL-C in a short time,” he said.

“Additional research must prove that this low LDL-C translates to reduction of MIs and strokes, and there is increasing evidence that this will happen,” Dr. Drexel noted.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Drexel had no financial conflicts to disclose.

SOURCE: Okada T et al. ESC 2020. JACC Cardiovascular Interventions. 2020 Aug 28. doi: 10.1016/j.jcin.2020.08.026.

Treatment with statins was associated with a reduced risk of a severe or fatal course of COVID-19 by 30%, a meta-analysis of four published studies has shown.

RogerAshford/Thinkstock

In the analysis that included almost 9,000 COVID-19 patients, there was a significantly reduced risk for fatal or severe COVID-19 among patients who were users of statins, compared with nonusers (pooled hazard ratio, 0.70; 95% confidence interval, 0.53-0.94).

Based on the findings, “it may be time we shift our focus to statins as the potential therapeutic options in COVID-19 patients,” authors Syed Shahzad Hasan, PhD, University of Huddersfield (England), and Chia Siang Kow, MPharm, International Medical University, Kuala Lumpur, Malaysia, said in an interview.

The study was published online August 11 in The American Journal of Cardiology.
 

Moderate- to good-quality data

The analysis included four studies published up to July 27 of this year. Eligible studies included those with a cohort or case-control designs, enrolled patients with confirmed COVID-19, and had data available allowing comparison of the risk of severe illness and/or mortality among statin users versus nonusers in adjusted analyses, the authors noted.

The four studies – one of “moderate” quality and three of “good” quality – included a total of 8,990 COVID-19 patients.

In the pooled analysis, there was a significantly reduced risk for fatal or severe COVID-19 with use of statins, compared with non-use of statins (pooled HR, 0.70; 95% CI, 0.53-0.94).

Their findings also “discredited the suggestion of harms with the use of statins in COVID-19 patients,” the authors concluded.

“Since our meta-analysis included a fairly large total number of COVID-19 patients from four studies in which three are large-scale studies that adjusted extensively for multiple potential confounding factors, the findings can be considered reliable,” Dr. Hasan and Mr. Kow wrote in their article.

Based on the results, “moderate- to high-intensity statin therapy is likely to be beneficial” in patients with COVID-19, they said.

However, they cautioned that more data from prospective studies are needed to substantiate the findings and to determine the appropriate regimen for a statin in COVID-19 patients.

Yibin Wang, PhD, of the University of California, Los Angeles, said that “this is a very simple meta-analysis from four published studies which consistently reported a protective or neutral effect of statin usage on mortality or severe complications in COVID-19 patients.”

Although the scope of this meta-analysis was “quite limited, the conclusion was not unexpected, as most of the clinical analysis so far reported supports the benefits or safety of statin usage in COVID-19 patients,” Dr. Wang said in an interview.
 

Nonetheless, questions remain

While there is “almost no dispute” about the safety of continuing statin therapy in COVID-19 patients, it remains to be determined if statin therapy can be implemented as an adjuvant or independent therapy and a part of the standard care for COVID-19 patients regardless of their hyperlipidemia status, said Dr. Wang, who was not associated with Dr. Hasan’s and Mr. Kow’s research.

“While statin usage is associated with several beneficial effects such as anti-inflammation and cytoprotection, these effects are usually observed from long-term usage rather than short-term/acute administration. Therefore, prospective studies and randomized trials should be conducted to test the efficacy of stain usage for COVID-19 patients with mild to severe symptoms,” he noted.

“Considering the excellent record of statins as a safe and cheap drug, it is certainly a worthwhile effort to consider its broad-based usage for COVID-19 in order to lower the overall death and severe complications,” Dr. Wang concluded.

Guillermo Rodriguez-Nava, MD, department of internal medicine, AMITA Health Saint Francis Hospital, Evanston, Ill., is first author on one of the studies included in this meta-analysis.

The retrospective, single-center study found slower progression to death associated with atorvastatin in older patients with COVID-19 admitted to the ICU. 

“Currently, there are hundreds of clinical trials evaluating a wide variety of pharmacological therapies for COVID-19. Unfortunately, these trials take time, and we are getting results in dribs and drabs,” Dr. Rodriguez-Nava said in an interview.

“In the meantime, the best available evidence is observational, and COVID-19 treatment regiments will continue to evolve. Whether atorvastatin is effective against COVID-19 is still under investigation. Nevertheless, clinicians should consider at least continuing them in patients with COVID-19,” he advised.

The study had no specific funding. Dr. Hasan, Mr. Kow, Dr. Wang, and Dr. Rodriguez-Nava disclosed no relationships relevant to this research.

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

Treatment with statins was associated with a reduced risk of a severe or fatal course of COVID-19 by 30%, a meta-analysis of four published studies has shown.

RogerAshford/Thinkstock

In the analysis that included almost 9,000 COVID-19 patients, there was a significantly reduced risk for fatal or severe COVID-19 among patients who were users of statins, compared with nonusers (pooled hazard ratio, 0.70; 95% confidence interval, 0.53-0.94).

Based on the findings, “it may be time we shift our focus to statins as the potential therapeutic options in COVID-19 patients,” authors Syed Shahzad Hasan, PhD, University of Huddersfield (England), and Chia Siang Kow, MPharm, International Medical University, Kuala Lumpur, Malaysia, said in an interview.

The study was published online August 11 in The American Journal of Cardiology.
 

Moderate- to good-quality data

The analysis included four studies published up to July 27 of this year. Eligible studies included those with a cohort or case-control designs, enrolled patients with confirmed COVID-19, and had data available allowing comparison of the risk of severe illness and/or mortality among statin users versus nonusers in adjusted analyses, the authors noted.

The four studies – one of “moderate” quality and three of “good” quality – included a total of 8,990 COVID-19 patients.

In the pooled analysis, there was a significantly reduced risk for fatal or severe COVID-19 with use of statins, compared with non-use of statins (pooled HR, 0.70; 95% CI, 0.53-0.94).

Their findings also “discredited the suggestion of harms with the use of statins in COVID-19 patients,” the authors concluded.

“Since our meta-analysis included a fairly large total number of COVID-19 patients from four studies in which three are large-scale studies that adjusted extensively for multiple potential confounding factors, the findings can be considered reliable,” Dr. Hasan and Mr. Kow wrote in their article.

Based on the results, “moderate- to high-intensity statin therapy is likely to be beneficial” in patients with COVID-19, they said.

However, they cautioned that more data from prospective studies are needed to substantiate the findings and to determine the appropriate regimen for a statin in COVID-19 patients.

Yibin Wang, PhD, of the University of California, Los Angeles, said that “this is a very simple meta-analysis from four published studies which consistently reported a protective or neutral effect of statin usage on mortality or severe complications in COVID-19 patients.”

Although the scope of this meta-analysis was “quite limited, the conclusion was not unexpected, as most of the clinical analysis so far reported supports the benefits or safety of statin usage in COVID-19 patients,” Dr. Wang said in an interview.
 

Nonetheless, questions remain

While there is “almost no dispute” about the safety of continuing statin therapy in COVID-19 patients, it remains to be determined if statin therapy can be implemented as an adjuvant or independent therapy and a part of the standard care for COVID-19 patients regardless of their hyperlipidemia status, said Dr. Wang, who was not associated with Dr. Hasan’s and Mr. Kow’s research.

“While statin usage is associated with several beneficial effects such as anti-inflammation and cytoprotection, these effects are usually observed from long-term usage rather than short-term/acute administration. Therefore, prospective studies and randomized trials should be conducted to test the efficacy of stain usage for COVID-19 patients with mild to severe symptoms,” he noted.

“Considering the excellent record of statins as a safe and cheap drug, it is certainly a worthwhile effort to consider its broad-based usage for COVID-19 in order to lower the overall death and severe complications,” Dr. Wang concluded.

Guillermo Rodriguez-Nava, MD, department of internal medicine, AMITA Health Saint Francis Hospital, Evanston, Ill., is first author on one of the studies included in this meta-analysis.

The retrospective, single-center study found slower progression to death associated with atorvastatin in older patients with COVID-19 admitted to the ICU. 

“Currently, there are hundreds of clinical trials evaluating a wide variety of pharmacological therapies for COVID-19. Unfortunately, these trials take time, and we are getting results in dribs and drabs,” Dr. Rodriguez-Nava said in an interview.

“In the meantime, the best available evidence is observational, and COVID-19 treatment regiments will continue to evolve. Whether atorvastatin is effective against COVID-19 is still under investigation. Nevertheless, clinicians should consider at least continuing them in patients with COVID-19,” he advised.

The study had no specific funding. Dr. Hasan, Mr. Kow, Dr. Wang, and Dr. Rodriguez-Nava disclosed no relationships relevant to this research.

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

Treatment with statins was associated with a reduced risk of a severe or fatal course of COVID-19 by 30%, a meta-analysis of four published studies has shown.

RogerAshford/Thinkstock

In the analysis that included almost 9,000 COVID-19 patients, there was a significantly reduced risk for fatal or severe COVID-19 among patients who were users of statins, compared with nonusers (pooled hazard ratio, 0.70; 95% confidence interval, 0.53-0.94).

Based on the findings, “it may be time we shift our focus to statins as the potential therapeutic options in COVID-19 patients,” authors Syed Shahzad Hasan, PhD, University of Huddersfield (England), and Chia Siang Kow, MPharm, International Medical University, Kuala Lumpur, Malaysia, said in an interview.

The study was published online August 11 in The American Journal of Cardiology.
 

Moderate- to good-quality data

The analysis included four studies published up to July 27 of this year. Eligible studies included those with a cohort or case-control designs, enrolled patients with confirmed COVID-19, and had data available allowing comparison of the risk of severe illness and/or mortality among statin users versus nonusers in adjusted analyses, the authors noted.

The four studies – one of “moderate” quality and three of “good” quality – included a total of 8,990 COVID-19 patients.

In the pooled analysis, there was a significantly reduced risk for fatal or severe COVID-19 with use of statins, compared with non-use of statins (pooled HR, 0.70; 95% CI, 0.53-0.94).

Their findings also “discredited the suggestion of harms with the use of statins in COVID-19 patients,” the authors concluded.

“Since our meta-analysis included a fairly large total number of COVID-19 patients from four studies in which three are large-scale studies that adjusted extensively for multiple potential confounding factors, the findings can be considered reliable,” Dr. Hasan and Mr. Kow wrote in their article.

Based on the results, “moderate- to high-intensity statin therapy is likely to be beneficial” in patients with COVID-19, they said.

However, they cautioned that more data from prospective studies are needed to substantiate the findings and to determine the appropriate regimen for a statin in COVID-19 patients.

Yibin Wang, PhD, of the University of California, Los Angeles, said that “this is a very simple meta-analysis from four published studies which consistently reported a protective or neutral effect of statin usage on mortality or severe complications in COVID-19 patients.”

Although the scope of this meta-analysis was “quite limited, the conclusion was not unexpected, as most of the clinical analysis so far reported supports the benefits or safety of statin usage in COVID-19 patients,” Dr. Wang said in an interview.
 

Nonetheless, questions remain

While there is “almost no dispute” about the safety of continuing statin therapy in COVID-19 patients, it remains to be determined if statin therapy can be implemented as an adjuvant or independent therapy and a part of the standard care for COVID-19 patients regardless of their hyperlipidemia status, said Dr. Wang, who was not associated with Dr. Hasan’s and Mr. Kow’s research.

“While statin usage is associated with several beneficial effects such as anti-inflammation and cytoprotection, these effects are usually observed from long-term usage rather than short-term/acute administration. Therefore, prospective studies and randomized trials should be conducted to test the efficacy of stain usage for COVID-19 patients with mild to severe symptoms,” he noted.

“Considering the excellent record of statins as a safe and cheap drug, it is certainly a worthwhile effort to consider its broad-based usage for COVID-19 in order to lower the overall death and severe complications,” Dr. Wang concluded.

Guillermo Rodriguez-Nava, MD, department of internal medicine, AMITA Health Saint Francis Hospital, Evanston, Ill., is first author on one of the studies included in this meta-analysis.

The retrospective, single-center study found slower progression to death associated with atorvastatin in older patients with COVID-19 admitted to the ICU. 

“Currently, there are hundreds of clinical trials evaluating a wide variety of pharmacological therapies for COVID-19. Unfortunately, these trials take time, and we are getting results in dribs and drabs,” Dr. Rodriguez-Nava said in an interview.

“In the meantime, the best available evidence is observational, and COVID-19 treatment regiments will continue to evolve. Whether atorvastatin is effective against COVID-19 is still under investigation. Nevertheless, clinicians should consider at least continuing them in patients with COVID-19,” he advised.

The study had no specific funding. Dr. Hasan, Mr. Kow, Dr. Wang, and Dr. Rodriguez-Nava disclosed no relationships relevant to this research.

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