Evolocumab Reduces Risk of Major Events in Patients Without Prior Cardiovascular History

In the phase 3, double-blind, randomized, placebo-controlled, global VESALIUS-CV clinical trial (NCT03872401), evolocumab (Repatha; Amgen) with a standard regimen of statins or other lipid-lowering therapy (LLT) significantly reduced the risk of major adverse cardiovascular events (MACE) in individuals without a prior history of heart attack or stroke, according to a news release from Amgen.^1,2

The trial, which enrolled 12,000 high-risk patients—85% of whom continued a high-intensity or moderate low-density lipoprotein cholesterol (LDL-C) reducing therapy—is a landmark development in establishing evolocumab as an agent for both primary and secondary cardiovascular disease (CVD) prevention.¹

Full results from VESALIUS-CV are slated to be presented at the 2025 American Heart Association Scientific Sessions and will subsequently be submitted to a peer-reviewed journal.¹

"These results mark an important milestone in the fight against cardiovascular disease, the leading cause of death worldwide. The benefit across endpoints and established safety profile underscore [evolocumab’s] role as a cornerstone therapy in comprehensive lipid management," Jay Bradner, MD, executive vice president of research and development at Amgen, said in the news release.¹

Specifics of the VESALIUS-CV Trial

VESALIUS-CV enrolled thousands of patients with known atherosclerotic cardiovascular disease (ASCVD) or high-risk diabetes but whom had no history of myocardial infarction and stroke and either LDL-C of 90 mg/dL or higher, non-high-density lipoprotein cholesterol of 120 mg/dL, or apolipoprotein B of 80 mg/dL or more. Patients also were required to be currently treated with an LLT. Randomization allotted patients to receive either evolocumab or placebo in addition to optimized LLT and were followed for a median of 4.5 years.¹

Primary end points of the trial were time to first occurrence of a composite of coronary heart disease (CHD) death, heart attack, or ischemic stroke, in addition to time to first occurrence of a composite of CHD death, heart attack, ischemic stroke, or any ischemia-driven arterial revascularization.¹

Both primary end points were successfully met and were statistically and clinically significant. In an especially positive development, no novel safety signals were observed across the large cohort.¹

What is Evolocumab?

Evolocumab is a human monoclonal antibody designed to inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), a secreted protease that mediates the LDL receptor. Research has validated PCSK9 as a valuable therapeutic target in CHD. Evolocumab binds to PCSK9 and prevents circulation of PCSK9 to the LDL receptor, which permits the receptor to recycle back to the liver cell surface. Therefore, there is an increased number of LDL receptors available to clear LDL-C from the blood.^1,3

The FDA first approved evolocumab in August 2015 to lower LDL-C in adults with heterozygous familial hypercholesterolemia or existing clinical ASCVD. Recently, the FDA expanded the indication to include adults at increased risk of MACE caused by uncontrolled LDL-C, aligning with the current study results, as patients no longer are required to have a prior diagnosis of CVD.^1,4

What Should Pharmacists Consider?

There is some pertinent safety information that pharmacists should counsel patients on, including the risk of serious hypersensitivity reactions such as angioedema, which has occurred in some patients treated with evolocumab. Pharmacists should ensure that, if there are signs or symptoms of serious hypersensitivity, treatment with evolocumab is promptly discontinued, with symptoms monitored until their resolution.¹

In the cardiovascular outcomes trial, the most common adverse reactions were diabetes mellitus, nasopharyngitis, and upper respiratory tract infection. Pharmacists should monitor patients throughout the duration of evolocumab’s administration. Furthermore, as with therapeutic proteins, immunogenicity is a possibility; patients should be counseled regarding this occurrence and appropriate steps if it occurs. With the clinical benefits of evolocumab affirmed over a decade of real-world practice, pharmacists can be assured of its efficacy and safety.¹

"[Evolocumab] is known as a highly effective LDL-C lowering treatment and is now the first and only PCSK9 inhibitor shown to reduce cardiovascular events in high-risk adults without prior heart attack or stroke,” Bradner continued. “These additional data demonstrate that [evolocumab] has the potential to reach tens of millions more patients earlier in their journey, before a life-altering event occurs."¹

REFERENCES

1. Landmark phase 3 trial (VESALIUS-CV) meets primary endpoints in a cardiovascular primary prevention study of 12,000 patients. Amgen. News release. Released October 2, 2025. Accessed October 14, 2025. https://www.amgen.com/newsroom/press-releases/2025/10/landmark-phase-3-trial-vesaliuscv-meets-primary-endpoints-in-a-cardiovascular-primary-prevention-study-of-12000-patients

2. Effect of evolocumab in patients at high cardiovascular risk without prior myocardial infarction or stroke (VESALIUS-CV). ClinicalTrials.gov Identifier: NCT03872401. Last Updated October 6, 2025. Accessed October 14, 2025. https://www.clinicaltrials.gov/study/NCT03872401

3. Horton J, Cohen J, Hobbs H. PCSK9: a convertase that coordinates LDL catabolism. JLR. 2009;50:S172-S177. doi:10.1194/jlr.R800091-JLR200

4. Ferruggia K. FDA expands evolocumab to treat adults at increased risk for major adverse cardiovascular events. Pharmacy Times. Published August 25, 2025. Accessed October 14, 2025. https://www.pharmacytimes.com/view/fda-expands-evolocumab-to-treat-adults-at-increased-risk-for-major-adverse-cardiovascular-events