Amgen has announced results from the phase 3 VESALIUS-CV clinical trial, which showed that Repatha (evolocumab) achieved statistically significant and clinically meaningful reductions in major adverse cardiovascular events (MACE) in high-risk adults without a prior heart attack or stroke, when added to statins or other low-density lipoprotein cholesterol (LDL-C)–lowering treatments.
Repatha is the first and only PCSK9 inhibitor to demonstrate a significant reduction of cardiovascular events as both high-risk primary and secondary prevention. The results were presented in a late-breaking session at the 2025 American Heart Association Scientific Sessions and simultaneously published in the New England Journal of Medicine.
In the study of more than 12,000 patients with atherosclerosis or diabetes who had no prior heart attack or stroke, Repatha demonstrated a 25% relative reduction in the risk of a composite of coronary heart disease (CHD) death, heart attack or ischemic stroke (3-P MACE), and 19% reduction in a broader composite that also included any ischemia-driven arterial revascularization (4-P MACE). Repatha also reduced the risk of heart attack by 36%. In a cohort of patients included in a lipid sub-study, the median achieved LDL-C was 45 mg/dL compared to 109 mg/dL in the placebo arm.
“The VESALIUS-CV results deliver clear and compelling evidence that intensive LDL-C lowering is critical to reducing cardiovascular risk,” said Jay Bradner, executive vice president of research and Development at Amgen.
“Repatha has once again demonstrated its ability to protect patients from the cardiovascular events they fear most, like heart attack or stroke, even before one occurs. These findings reinforce the urgent need to translate today’s evidence into tomorrow’s clinical practice. With a decade of real-world experience and proven benefit across the continuum of cardiovascular disease, every patient facing elevated risk due to uncontrolled LDL-C should be considered for Repatha.”
Repatha significantly reduced the risk of most secondary endpoints, including the following composites: heart attack, ischemic stroke or any ischemia-driven revascularization; CHD death, heart attack or revascularization; cardiovascular death, heart attack or ischemic stroke; and CHD death or heart attack. In addition, there were numerical trends for reduced mortality rates in the Repatha arm, including cardiovascular death (21% relative risk reduction), CHD death (11% relative risk reduction) and all-cause death (20% relative risk reduction), as well as a trend toward lower ischemic stroke (21% relative risk reduction).
“Building on the success of FOURIER, in which we showed that adding evolocumab to statin therapy in patients with a prior heart attack or stroke reduced the risk of subsequent major adverse cardiovascular events, we now show that in the much larger population of patients with atherosclerosis or diabetes, but without a prior heart attack or stroke, that adding evolocumab to their lipid regimen substantially reduces their risk of MACE,” said Marc S. Sabatine, chair of the TIMI Study Group and the Lewis Dexter, MD, endowed chair in cardiovascular medicine at Brigham and Women’s Hospital.
“In both FOURIER and VESALIUS-CV, patients in the evolocumab arm achieved median LDL-C levels in the range of approximately 30 to 45 mg/dL, supporting such a target across a broad range of patients.”
Results also showed reduction in risk of cardiovascular events in the nearly 60% of trial participants who had diabetes, reinforcing the urgent need to manage LDL-C in these patients who remain largely undertreated.
“Cardiovascular disease remains the leading cause of mortality and morbidity for people living with diabetes, driven by risk factors including high LDL-C. Reducing this risk needs to be prioritized in primary care settings where the majority of people living with diabetes receive care,” said Osagie Ebekozien, chief quality officer, American Diabetes Association.
“The American Diabetes Association is committed to transforming diabetes care through the implementation of evidence-based guidelines for managing hyperlipidemia and reducing cardiovascular risk.”
No new safety signals were identified, and tolerability was consistent with the current prescribing information in the US. Only treatment-emergent adverse events that were serious or led to discontinuation were captured.
Cardiovascular disease is the leading cause of death worldwide.1 Every 40 seconds, a heart attack or stroke occurs in the U.S., and 75% of those are first-time events. Recent research shows that more than 99% of people who experience a first-time cardiovascular event have at least one traditional risk factor, including high LDL-C which is one of the most modifiable risk factors for heart attack or stroke.
Repatha was first approved in 2015 and has since been used by more than 6.7m patients globally. Earlier this year, the U.S. Food and Drug Administration broadened the approved use of Repatha to include adults at increased risk for major adverse CV events due to uncontrolled LDL-C. All US patients can now access Repatha through AmgenNow, the company’s direct-to-patient program, at a monthly price of $239, nearly 60% lower than the current US list price.
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