Evolocumab Lowers Risk of Heart Attacks by 20% Compared With Ezetimibe in a Large Real-World Study

Findings Represent Largest and Most Rigorous Head-to-Head Real-World Outcomes Analysis of Repatha and Ezetimibe 

Study Examined More Than Half a Million Adults Living with Heart Disease

Results Provide Important New Clinical Evidence to Inform Non-Statin Treatment Decisions for Patients 

THOUSAND OAKS, Calif. -- Amgen announced results from a large real-world study showing that treatment with Repatha^® (evolocumab) reduced the risk of fatal or nonfatal heart attacks by 20% compared with ezetimibe in people with atherosclerotic cardiovascular disease (ASCVD) and prior statin use. The study followed more than 544,000 adults for up to four years. The findings were published in The American Journal of Preventive Cardiology.

"We have known for decades that lowering LDL cholesterol reduces cardiovascular risk, yet many patients with ASCVD cannot reach recommended levels with statins alone," said Paul Burton, MD, PhD, chief medical officer at Amgen. "For physicians deciding what treatment to add next, whether that's prescribing patients Repatha or ezetimibe, this large real-world study provides clear evidence to help inform that choice. Patients who received Repatha had a 20% lower risk of heart attack or death from a heart attack compared with those who received ezetimibe."

Among patients with a baseline low-density lipoprotein cholesterol (LDL-C) measurement (N = 225,048), the four-year cumulative risk of heart attack was lower with Repatha than with ezetimibe, an oral medicine that lowers LDL-C by limiting cholesterol absorption (5.88% vs. 7.76%). The analysis compared cardiovascular outcomes across a large patient population using rigorous analytical methods. The study is distinctive in its scale and approach to analyzing outcomes in the real world, requiring precise investigative methods to provide a large, practical evidence base that evaluates cardiovascular outcomes between the two treatments. Its findings provide a practical real-world complement to clinical trial evidence and may help inform clinical practice.

"While the recent ACC/AHA Multisociety Guideline update recognizes both ezetimibe and PCSK9 inhibitors like evolocumab as non-statin options for patients with ASCVD, clinicians have lacked direct cardiovascular outcomes evidence to help inform treatment choices for their patients that may allow them to fully achieve the recommended LDL-C goals of <70 mg/dL and <55 mg/dL," said Nihar Desai, MD, MPH, associate professor of medicine and vice chief of the Section of Cardiovascular Medicine, Yale University School of Medicine. "These findings provide important comparative data that can help clinicians distinguish between these treatment options and make more informed choices to reduce their patients' cardiovascular risk."

This real-world study used a rigorous design that mirrors a randomized clinical trial to compare cardiovascular outcomes among adults with ASCVD who initiated Repatha or ezetimibe in routine U.S. clinical practice. The analysis leveraged de-identified data from the Komodo Healthcare Map^® and applied a robust analytical approach to ensure that the two treatment groups were as similar as possible with respect to their baseline patient characteristics.

About the Real-World Comparative Study
The Real-World Comparative Effectiveness of Evolocumab Versus Ezetimibe in Adults with Atherosclerotic Cardiovascular Disease: An Active-Comparator New-User Study is a non-interventional, active-comparator, new-user cohort study that applied a target trial framework to compare cardiovascular outcomes among adults with ASCVD and prior statin use who initiated evolocumab or ezetimibe in routine U.S. clinical care. The study included 544,103 adults identified in the Komodo Healthcare Map^® database, including 64,421 who initiated evolocumab and 479,682 who initiated ezetimibe between 2017 and 2024, with follow-up through June 2026. The primary outcome was fatal or nonfatal myocardial infarction (MI) over up to four years of follow-up.

Treatment with evolocumab lowered the rate of fatal or nonfatal MI by 20% compared with ezetimibe (HR, 0.80; 95% CI, 0.70-0.91). Among patients without an available baseline LDL-C measurement, the corresponding four-year cumulative risks were 5.65% and 7.06%, respectively. The study used inverse probability weighting to balance measured baseline characteristics between treatment groups and a calibrated estimator to account for incomplete availability of baseline LDL-C; a prespecified sensitivity analysis that continued follow-up regardless of changes in background statin therapy produced consistent results.

Amgen's Commitment to Cardiovascular Innovation
Cardiovascular disease (CVD) remains a major global health threat, linked to multiple interrelated risk factors like high LDL-C, Lp(a), obesity, diabetes and hypertension.^1,2 These risks often coexist and require a comprehensive approach to prevention and care. Amgen is taking bold action, building on decades of leadership in CVD through LDL-C management to advance additional innovative, investigational treatments in the pipeline targeting common drivers of CVD. By combining scientific innovation with strategic partnerships to drive earlier testing, better care and broader access, Amgen's efforts reflect a sustained commitment to advancing both the science and the system of CV care.

Amgen's Center for Observational Research
Amgen's Center for Observational Research (CfOR) is a global, multidisciplinary organization dedicated to bringing epidemiologic and data science expertise together with real-world data (RWD) to generate evidence that advances Amgen's mission to serve patients. Across the medicine lifecycle, CfOR helps deepen understanding of disease and how care is delivered in clinical practice, evaluate the comparative effectiveness and safety of Amgen's medicines, and accelerate the development of innovative therapies. By paving the way for groundbreaking applications of RWD and real-world evidence (RWE), CfOR is helping progress the science that informs healthcare decision-making and deliver meaningful benefit for patients and the broader healthcare community. 

About Repatha
Repatha is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). Repatha binds to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein (LDL) receptor (LDLR), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, Repatha increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.

Repatha is one of the most extensively studied PCSK9 inhibitors, with clinical and real-world evidence across diverse populations and CV risk profiles.² The clinical benefits and safety of Repatha have been studied for 15 years in 51 clinical trials with over 57,000 patients.³ Repatha is the only PCSK9 inhibitor to demonstrate a significant reduction of cardiovascular events as both high-risk primary and secondary prevention, with patients achieving and maintaining dramatic LDL-C reductions using Repatha once every two weeks.^4,5

Repatha was first approved in 2015 and has since been used by approximately 9 million patients globally.⁶ In August 2025, 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. In August 2026, the European Commission approved an expanded indication for the use of Repatha in adults with established or high risk for ASCVD to reduce CV risk by lowering LDL-C levels, as an adjunct to correction of other risk factors, based on results from the Phase 3 VESALIUS-CV trial. Repatha is approved in 75 countries, including the U.S., Japan, Canada and in all 28 countries that are members of the European Union.⁷ Applications in other countries are pending. Repatha is the most covered PCSK9 inhibitor monoclonal antibody in the U.S.⁸ ~96% of patients are covered for Repatha across insurance types, with most patients paying less than $50/month.⁹ Through AmgenNow™, a direct-to-patient program, Repatha is available to patients at nearly 60% below the monthly list price.

References

1. Vasan RS, Enserro DM, Xanthakis V, Beiser AS, Seshadri S. Temporal trends in the remaining lifetime risk of cardiovascular disease among middle-aged adults across 6 decades: the Framingham Study. Circulation. 2022:145(17):1324-1338. https://doi.org/10.1161/CIRCULATIONAHA.121.057889
2. Tsimikas S, Marcovina S. Ancestry, lipoprotein(a), and cardiovascular risk thresholds: JACC Review Topic of the Week. JACC. 2022;80(9):934-946. https://doi.org/10.1016/j.jacc.2022.06.019
3. Data on File; Amgen, 2025.
4. Ndumele CE, Blumenthal RS. VESALIUS and the anatomy of high-risk prevention. N Engl J Med. 2026;394(2):191-193. doi: 10.1056/NEJMe2515447
5. Marston NA, Bohula EA, Bhatia AK, 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. 2026;335(16):1400-1407. doi: 10.1001/jama.2026.3277
6. Data on File; Amgen, 2026.
7. Data on File; Amgen, 2025.
8. Data on File; Amgen, 2026.
9. Data on File; Amgen, 2026.

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