Mass General Brigham researchers found that the intensive cholesterol‑lowering therapy evolocumab reduced the risk of a first major cardiovascular event in high‑risk patients who did not have known atherosclerosis (the build-up of plaque inside artery walls) but did have diabetes. Results were presented at the American College of Cardiology's Annual Scientific Session & Expo and simultaneously published in JAMA.
"For over a decade, the intensive cholesterol‑lowering have been reserved for patients who already have cardiovascular disease," said corresponding author Nicholas A. Marston, MD, MPH, a cardiologist with the Mass General Brigham Heart and Vascular Institute. "These results demonstrate the benefit of intensive lowering cholesterol earlier and should change how we think about the prevention of heart attacks, strokes, and heart disease in patients without known significant atherosclerosis."
Cardiovascular disease remains the leading cause of death worldwide. Lowering low‑density lipoprotein cholesterol (LDL‑C), often called "bad cholesterol," is a key strategy for reducing risk. Evolocumab, a potent PCSK9 inhibitor, reduces LDL-C by approximately 60%, and is additive to the effect of statins. Currently, people who don't have atherosclerosis but are at high risk are commonly prescribed statins, if they are prescribed cholesterol-lowering medications at all.
In a subgroup analysis of the VESALIUS-CV randomized trial, sponsored by Amgen Inc., researchers evaluated whether evolocumab could prevent cardiovascular events in 3,655 patients without significant atherosclerosis and with high-risk diabetes. High-risk diabetes was defined as diabetes with a duration of at least 10 years, diabetes that required daily insulin use, or diabetes with microvascular disease.
Participants were treated with evolocumab injections every two weeks or placebo. Patients in both arms also continued standard cholesterol-lowering therapy, including statins and ezetimibe.
Patients receiving evolocumab achieved substantially lower cholesterol levels during the trial. After 48 weeks, median LDL‑C levels were about 51% lower in the evolocumab group compared with the placebo (52 mg/dL versus 111mg/dL).
Over a median follow‑up of nearly five years, the patients receiving evolocumab on top of standard cholesterol-lowering therapy had a 31% lower risk of a first major cardiovascular event, compared with the patients treated with standard cholesterol-lowering therapy alone. Events included coronary heart disease death, heart attack, or ischemic stroke. Five‑year event rates were 5% among patients receiving evolocumab compared with 7.1% among those receiving placebo.
Serious adverse events occurred at similar rates in both the evolocumab and placebo groups, suggesting the treatment was well tolerated in this population.
The investigators note that future studies will be important to determine whether similar benefits extend to other groups of high‑risk patients without established atherosclerosis.
Authorship: In addition to Marston, Mass General Brigham authors include Erin A. Bohula, Jeong-Gun Park, Sabina A. Murphy, Ron Blankstein, 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, Lyrica Liu, Subodh Verma, Naveed Sattar, Stephen J. Nicholls, Jose Lopez-Sendon, Ioanna Gouni-Berthold, Lale Tokgozoglu, Marcoli Cyrille, and Gabriel Paiva da Silva Lima.
Disclosures: Marston, Bohula, Kuder, Park, Murphy, Giugliano, and Sabatine are members of the TIMI Study Group. The TIMI Study Group reports grant support through Brigham and Women's Hospital from Amgen and other pharmaceutical companies. Marston, Bohula, De Ferrari, Nicolau, Gouni-Berthold Tokgozoglu, Giugliano, and Sabatine report personal fees from Amgen. Bhatia, Walsh, Liu, Cyrille, and Paiva da Silva Lima are employees and stockholders of Amgen. Blankstein reports research support and consulting fees from Amgen Inc. Giugliano reports honoraria for lectures and CME programs from Amgen. Additional author disclosures can be found in the paper.
Funding: Amgen Inc.
Paper cited: Marston N initial et al. "Evolocumab to Reduce First Major Cardiovascular Events in Patients without Known Significant Atherosclerosis and with Diabetes: Results from the VESALIUS-CV trial" JAMA DOI: 10.1001/jama.2026.3277
