Real-World Effectiveness of Evolocumab in Reducing Major Adverse Cardiovascular Events: A Cohort Study.

BACKGROUND: Evolocumab reduces major adverse cardiovascular events in randomized trials, but evidence of its effectiveness in real-world clinical practice remains limited. METHODS: US adults with atherosclerotic cardiovascular disease who initiated evolocumab between 2017 and 2023 were identified from the Komodo Healthcare Map. At day 75 after initiation (index date), patients were classified as treated (remained on evolocumab) or nontreated (discontinued evolocumab before day 75). Patients were followed until the earliest of outcome occurrence, evolocumab discontinuation (treated group) or reinitiation (nontreated group), insurance disenrollment, end of database, or death. The primary outcome was a composite of myocardial infarction, stroke, or coronary revascularization; the secondary outcome was a composite of myocardial infarction, stroke, or cardiovascular disease death. Four-year cumulative incidence, risk ratios (RR), and 95% CIs were estimated, adjusting for confounders and informative censoring using inverse probability of treatment and censoring weights. Negative control outcomes were used to assess residual confounding before initiating comparative outcome analyses. RESULTS: After weighting, baseline characteristics were well balanced between treated (n=87 102) and nontreated (n=24 609) groups. At 4 years, treated patients had a 20% lower risk of the primary outcome (RR, 0.80 [95% CI, 0.73-0.86]) and a 29% lower risk of the secondary outcome (RR, 0.71 [95% CI, 0.64-0.78]) compared with nontreated patients. CONCLUSIONS: In a large, diverse, real-world population with atherosclerotic cardiovascular disease, evolocumab use was associated with significant reductions in major adverse cardiovascular events, supporting the effectiveness of guideline-recommended PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor therapy in routine clinical practice.