Researchers from Mass General Brigham have unveiled the results of a large clinical trial that found that adding the drug evolocumab to patients' treatment significantly reduced the risk of major adverse cardiovascular events in those who are at high risk. Results were presented today at the American Heart Association Scientific Sessions and simultaneously published in The New England Journal of Medicine.
"The results of this trial offer hope for preventing a first heart attack, stroke, or other cardiovascular event in patients who are at high risk," said corresponding author Erin Bohula, MD, a cardiologist in the Mass General Brigham Heart and Vascular Institute. "Our findings reflect the promise of prevention strategies and reflect our ongoing commitment to conducting rigorous clinical trials to advance patient care with the goal of saving lives and improving quality of life."
PCSK9 inhibitors, such as evolocumab, are designed to reduce LDL cholesterol, a major risk factor for cardiovascular events. Previous studies have found that PCSK9 inhibitors can prevent subsequent cardiovascular events in patients who have previously had a heart attack or stroke, but the current study—known as The Effect of EVolocumab in PatiEntS at High CArdiovascuLar RIsk WithoUt Prior Myocardial Infarction or Stroke (VESALIUS)-CV trial—is the first to study the drug's preventive effects in people who have not previously had a heart attack or stroke.
The phase 3 trial was designed by the TIMI Study Group at Mass General Brigham, in conjunction with the trial sponsor and funder, Amgen, Inc. Participants who were enrolled from around the world had to have atherosclerosis or diabetes and LDL cholesterol levels above 90mg/dL. Importantly, participants were not eligible if they had previously had a heart attack or stroke. A total of 12,257 participants were randomly assigned to receive evolocumab (140 mg every two weeks) or a placebo, in addition to their standard care.
Participants were followed for a median of 4.6 years. During that time, 336 patients (6.2%) in the group that received evolocumab and 443 patients (8.0%) in the group that received placebo experienced coronary heart disease death, myocardial infarction, or ischemic stroke. Overall, this translates this to a 25% reduction in risk of one of these events. Moreover, the researchers report that compared to placebo, those taking evolocumab had a 36% reduction in heart attacks. In addition, a nominally lower rate of death was seen in the evolocumab arm (7.9% vs. 9.7%)
The authors note that while most patients in the trial were taking high-intensity statins or other cholesterol-lowering medications, some participants were on less intensive treatments or none at all. However, results were consistent regardless of patients' other treatments. Most patients in the study were white, meaning that results may not be generalizable to all patient populations.
"In VESALIUS-CV, patients in the evolocumab arm achieved LDL-C levels of around 40 mg/dL. I believe that is what we should be targeting in these patients," said Marc S. Sabatine, MD, MPH, Chair of the TIMI Study Group and the Lewis Dexter, MD, Endowed Chair in Cardiovascular Medicine at Brigham and Women's Hospital.
Authorship: In addition to Bohula, Mass General Brigham authors include Nicholas A. Marston, Jeong-Gun Park PhD1, Julia F. Kuder, Sabina A. Murphy, Robert P. Giugliano, and Marc S. Sabatine. Additional authors include Ajay K. Bhatia, Gaetano M. De Ferrari, Lawrence A. Leiter, Jose C. Nicolau, Emileigh Walsh, Huei Wang, Vladimir Blaha, Andrzej Budaj, Jan H. Cornel, Assen Goudev, Robert Gabor Kiss, Alberto J. Lorenzatti, Alexander Parkhomenko, Marcoli Cyrille, Gabriel Paiva da Silva Lim, and E. Magnus Ohman.
Disclosures:
Bohula and Sabatine are members of the TIMI Study Group. The TIMI Study Group reports grant support through Brigham and Women's Hospital from Abbott, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc., AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Ionis Pharmaceuticals, Inc., Marea; Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Saghmos Therapeutics, Siemens Healthcare Diagnostics, Inc., Softcell Medical Limited, Verve Therapeutics, and Zora Biosciences.
Bohula reports personal fees from Amgen, Celecor, Esperion, Kowa, Novo Nordisk, Servier, and Scleroderma Research Foundation. Sabatine reports personal fees from Amgen; AMPEL BioSolutions; Anthos Therapeutics; AstraZeneca; Beren Therapeutics; Boehringer Ingelheim; Canadian Cardiovascular Research Network; Dr. Reddy's Laboratories; General Medicines; Merck; North American Thrombosis Foundation; Novo Nordisk; Precision BioSciences; and TigerMed.
Funding: Funded by Amgen, Inc.
Paper cited: Bohula EA et al. "Evolocumab in Patients without Prior Myocardial Infarction or Stroke" NEJM DOI: 10.1056/NEJMoa2514428
