Amgen has published new data demonstrating that adding the cholesterol-lowering drug Repatha (evolocumab) to standard therapy significantly reduces the risk of a first major cardiovascular event in high-risk patients.

The Phase III VESALIUS-CV study (NCT03872401) found that Repatha, a PCSK9 inhibitor, cut the relative risk of a first major adverse cardiovascular event (MACE) by 25% compared to a placebo in patients who had not yet experienced a heart attack or stroke.

The findings were presented at the American Heart Association’s Scientific Sessions 2025, which took place from 7-10 November 2025, and simultaneously published in the New England Journal of Medicine.

Trial Design and Key Outcomes

VESALIUS-CV was a global, double-blind, randomized trial involving over 12,000 adults with either atherosclerosis or diabetes, but no prior history of heart attack or stroke. All participants had uncontrolled low-density lipoprotein cholesterol (LDL-C) despite being on statins or other lipid-lowering therapies. They were followed for a median of 4.6 years.

The study met its primary endpoint, showing a 25% relative risk reduction in a composite of coronary heart disease death, heart attack, or ischemic stroke. A key secondary endpoint, which also included ischemia-driven revascularization, was reduced by 19%. Perhaps most notably, the risk of a first heart attack was slashed by 36%.

The drug’s efficacy in lowering cholesterol was profound. In a lipid sub-study, patients receiving Repatha achieved a median LDL-C level of 45 mg/dL, compared to 109 mg/dL in the placebo group.

A Shift to Proactive Prevention

The significance of the VESALIUS-CV trial lies in its focus on primary prevention—stopping a first heart attack or stroke from ever occurring. Until now, robust evidence for PCSK9 inhibitors was largely confined to secondary prevention in patients who had already suffered a cardiovascular event.

“This trial showed a lot of benefit in those people who had not yet had an event,” said Dr. Michael Gibson, an interventional cardiologist and professor at Harvard Medical School. He used a powerful analogy to explain the shift: “We often take care of patients after they’ve had the car accident. And then we put the seatbelt on afterwards. I mean, these are people who haven’t had an accident yet. Kind of put the seatbelt on before they have the accident. Just because they haven’t had an event does not mean they’re not going to have an event.”

Dr. Carel le Roux, a professor of metabolic medicine at University College Dublin, noted: “My initial impression was that this is going to change my clinical practice, because now we actually have the data to show that for patients who have not yet had an event, we can drive down the risk”. Adding, “And it’s not only the relative risk that goes down. The absolute risk is very impressive.”

Dr. le Roux also highlighted the benefit seen in his specific patient population. “I have a lot of patients who have the disease of obesity and many of the complications of obesity, those metabolic complications such as type two diabetes, dyslipidemia, hypertension, and I was impressed with this study, is that we see all of those subgroups having significant benefit.”

Broader Implications and Safety

The trial also showed positive trends in reducing mortality, including a 21% relative risk reduction in cardiovascular death and a 20% reduction in all-cause death, though these did not reach statistical significance. No new safety signals were identified, with Repatha’s tolerability consistent with its known profile.

In a statement, Dr. Jay Bradner, Executive Vice President of R&D at Amgen, said the results “deliver clear and compelling evidence that intensive LDL-C lowering is critical to reducing cardiovascular risk.” He emphasized the urgency “to translate today’s evidence into tomorrow’s clinical practice.”

Repatha is one of the highest-grossing drugs for Amgen. It grossed $2.2 billion in sales last year, up 36% from 2023. The monoclonal antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9) is approved for the treatment of familial hypercholesterolemia (heterozygous and homozygous), and to reduce the risk of major adverse cardiovascular events in at-risk adults. The recent data position it as the first PCSK9 inhibitor with proven efficacy for both high-risk primary and secondary prevention.