Subanalysis suggests drug could be used for primary prevention of major cardiac events in broader group of patients

NEW ORLEANS (March 28, 2026) — The cholesterol-lowering therapy evolocumab reduced the risk of major adverse cardiac events by nearly one-third among patients who had no known significant atherosclerosis and had diabetes, according to a study presented at the American College of Cardiology’s Annual Scientific Session (ACC.26).

The study, a subgroup analysis of the VESALIUS-CV trial, involved over 3,600 patients with diabetes who were not previously known to have a significant buildup of plaque in the heart’s arteries (atherosclerosis), which can lead to heart attacks and stroke. Previous trials have demonstrated that intensively reducing low-density lipoprotein cholesterol (LDL-C) using PCSK9 inhibitors such as evolocumab on top of optimally tolerated statin therapy can be used as part of secondary prevention efforts to reduce cardiovascular risk in patients who have previously suffered a major cardiac event. VESALIUS-CV was the first trial to assess evolocumab’s use in high-risk primary prevention, focusing on patients who had not previously experienced a major cardiac event.

“I think this study changes the paradigm,” said Nicholas Marston, MD, MPH, a cardiologist and assistant professor of medicine at Brigham and Women’s Hospital and Harvard Medical School in Boston and the study’s lead author. “In current practice, PCSK9 inhibitors are largely reserved for patients who have had a prior heart attack or stroke, but here we see a benefit of using evolocumab not only to treat patients without a history of heart attack or stroke, but without known significant atherosclerosis. It’s a message to physicians and patients that we don’t have to wait until someone has atherosclerosis to treat them intensively. We can—and should—be much more proactive.”

Evolocumab is an injectable monoclonal antibody that works by blocking the PCSK9 protein, which increases the number of low-density lipoprotein receptors in the liver to more effectively remove LDL-C from the bloodstream. By substantially reducing LDL-C, a major contributor to plaque buildup, it helps to slow the progression of atherosclerosis, thereby preventing serious cardiac events.

The VESALIUS-CV trial enrolled 12,257 patients with an LDL-C of 90 mg/dL or higher and known atherosclerosis or diabetes and who had not had a prior heart attack or stroke. Results reported in 2025 showed evolocumab significantly reduced the risk of a first major adverse cardiac event compared with placebo in the full study population. For this new subgroup analysis, researchers analyzed outcomes in 3,655 VESALIUS-CV participants who did not have known significant atherosclerosis and who had diabetes. The median age of these participants was 65 years, 57% were female and 93% were White. In addition, 87% of patients were taking a statin.

The subgroup study had two co-primary endpoints: a composite of death from coronary heart disease, heart attack or ischemic stroke and a composite of any of these three outcomes or a procedure to open blocked arteries (revascularization) driven by reduced blood flow (ischemia). At a median of 4.8 years, the rate of both of these composite endpoints was 31% lower among patients receiving evolocumab compared with those receiving the placebo. The reduction in risk was apparent at the one-year mark, and the between-group differences increased to around 40% after the first year.

In patients who had their lipid levels checked throughout the study (about 550 of the 3,655 participants), those receiving evolocumab had a marked reduction in LDL-C—down to a median of 52 mg/dL at 48 weeks and 44 mg/dL at 96 weeks compared with 111 mg/dL and 105 mg/dL, respectively, among those taking placebo. These patients also were 32% less likely to die from cardiovascular causes and 24% less likely to die from any cause during the study period compared with the control group, although statistical significance was not assessed for these endpoints.

Based on the results of the full VESALIUS-CV trial and the subgroup analyses, researchers said primary care providers could consider using evolocumab in a much broader population of patients than has typically been the case. Marston said the findings underscore that patients with high cardiovascular risk appear to benefit from more intensive LDL-C-lowering treatment, even without known significant atherosclerosis, according to researchers.

“Over the decades, we’ve moved to lower and lower LDL-C goals, and we’ve continued to see benefit. Now, we’re in this process of moving earlier and earlier in the disease course, and so far, we’re continuing to see benefit from that approach,” he said.

The ACC/AHA Guideline on the Management of Dyslipidemia, released earlier this month, recommends lower LDL-C levels earlier in life. The guideline also brings back recommendations for LDL-C and non-HDL treatment goals to guide lipid-lowering therapy. The results from this subgroup analysis strongly support that in these lower-risk patients we should be targeting even lower LDL-C goals that are typically reserved for very high-risk secondary prevention patients, Marston said.

Marston said that it is possible that some participants who were included in the subgroup analysis had undiagnosed atherosclerotic heart disease since coronary imaging was not required for study enrollment. However, this reflects clinical practice in which routine coronary imaging is not recommended. The analysis was also limited to patients with diabetes, and the study population was primarily older adults and predominantly White. Researchers said that additional studies could elucidate whether evolocumab brings similar benefits for younger patients or those who have other cardiovascular risk factors but not diabetes.

The study was funded by Amgen, maker of evolocumab.

This study was simultaneously published online in JAMA at the time of presentation.

Marston will present the study, “Evolocumab Reduces Risk of First Major Cardiovascular Events by 31% in Patients without Significant Atherosclerosis: Results from VESALIUS-CV,” on Saturday, March 28, at 3:45 p.m. CT / 20:45 UTC in the Main Tent, Great Hall.  

ACC.26 will take place March 28-30, 2026, in New Orleans, bringing together cardiologists and cardiovascular specialists from around the world to share the newest discoveries in treatment and prevention. Follow @ACCinTouch, @ACCMediaCenter and #ACC26 for the latest news from the meeting.

The American College of Cardiology (ACC) is the global leader in transforming cardiovascular care and improving heart health for all. As the preeminent source of professional medical education for the entire cardiovascular care team since 1949, ACC credentials cardiovascular professionals in over 140 countries who meet stringent qualifications and leads in the formation of health policy, standards and guidelines. Through its world-renowned family of JACC Journals, NCDR registries, ACC Accreditation Services, global network of Member Sections, CardioSmart.org patient resources and more, the College is committed to ensuring a world where science, knowledge and innovation optimize patient care and outcomes. Learn more at ACC.org.

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