RWE Demonstrates Significant Four-Year MACE Reduction
Repatha (Evolocumab), Amgen’s PCSK9 inhibitor, has once again demonstrated its cardiovascular impact, this time in a real-world population exceeding 110,000 patients. New findings presented at the American Heart Association Scientific Sessions 2025 show that the therapy delivers sustained, long-term reductions in major adverse cardiovascular events (MACE) for patients with established atherosclerotic cardiovascular disease (ASCVD), extending the clinical narrative well beyond controlled trial settings.
The REPATHA-CE study, conducted by Target RWE in partnership with Amgen, is the largest real-world comparative effectiveness evaluation of evolocumab to date. Drawing on Komodo Health’s Healthcare Map®, which captures de-identified medical interactions for more than 330 million U.S. patients, the study examined outcomes across 87,102 individuals treated with Repatha and 24,609 matched controls between 2017 and 2023.
What You Need To Know
- Largest real-world study of Repatha (110,000+ patients) shows 20–29% MACE reduction over four years.
- Analysis confirms and extends FOURIER outcomes in a broad, real-world ASCVD population.
- Findings used Target RWE’s causalStudio platform and Komodo’s Healthcare Map data.
- Results strengthen clinical and payer rationale for aggressive LDL-C control.
Real-world data confirm and extend FOURIER outcomes
The analysis revealed a 20% reduction in the composite MACE endpoint of myocardial infarction (MI), stroke, and coronary revascularization for patients treated with Repatha. Even more striking was the 29% reduction in the composite of MI, stroke, and cardiovascular death at four years compared with patients who did not receive the drug.
These real-world reductions closely track the profile seen in FOURIER, Amgen’s pivotal outcomes trial, which originally demonstrated evolocumab’s ability to reduce cardiovascular events over a median follow-up of 2.2 years. The new findings extend that evidence to a broader, more heterogeneous patient population and over a notably longer duration.
Target RWE employed its causalStudio™ analytical platform to reduce bias and improve attribution across treatment arms. The inclusion of a large control cohort, sourced from real-world settings rather than a trial environment, gives the results a level of external validity that traditional randomized controlled trials cannot fully replicate.
“This study characterizes the long-term effectiveness of Repatha in reducing MACE in patients with ASCVD,” said M. Alan Brookhart, PhD, Senior Scientific Advisor at Target RWE. “It is compelling to see the benefits observed in the FOURIER trial reflected in a real-world patient population treated with Repatha.”
The RWE approach also captures patients with broader comorbidity profiles, cross-specialty care pathways, and varying adherence behaviours, variables that often dilute or distort expected outcomes in real-world therapeutic use. Despite that complexity, the magnitude of benefit remained robust across endpoints.
Amgen’s U.S. Medical Therapeutic Area Head, Dr. Leandro Boer, emphasized the practical implications: “Clinical trials have demonstrated Repatha’s ability to significantly reduce the risk of major cardiovascular events in adults at high-risk. This analysis confirms those benefits in everyday care.”
Boer further underscored the urgency of achieving guideline-aligned LDL-C targets. Despite longstanding recommendations, a large proportion of high-risk ASCVD patients fail to reach optimal LDL-C levels with statins alone. Real-world outcomes showing sustained reductions in MI, stroke, and cardiovascular death provide fresh weight to clinical and payer arguments for intensifying lipid-lowering therapy.
RWE’s expanding role in cardiovascular therapeutic strategy
The REPATHA-CE findings arrive at a moment when cardiovascular RWE is exerting increasing influence on payer decisions, outcomes-based contracts, and therapy sequencing. As more payers adopt retrospective and prospective RWE frameworks to guide coverage, large-scale analyses like this one serve as critical inputs into formulary and utilization management strategies.
For Amgen, the study deepens the evidence footprint at a time when PCSK9 inhibitors are competing within a more crowded LDL-C lowering landscape. For Target RWE, the project demonstrates the scalability and rigor of real-world causal inference tools in high-stakes therapeutic categories.
The results also reinforce a central therapeutic message in ASCVD care: aggressive LDL-C lowering, sustained over time, can meaningfully reduce the rate of life-altering cardiovascular events.
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