Impact of Evolocumab on LDL‐Cholesterol and Cardiovascular Outcomes in Patients With Established CVD: Systematic Review and Meta‐Analysis

BACKGROUND: Atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality, and many high-risk patients fail to reach LDL-cholesterol (LDL-C) targets on statins alone. Evolocumab, a PCSK9 inhibitor, offers potent LDL-C lowering, but a synthesis of its lipid and clinical benefits in secondary prevention is needed. METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials evaluating evolocumab in adults with established cardiovascular disease. PubMed, Embase, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov were searched through April 2025. Outcomes included lipid parameters, major adverse cardiovascular events (MACE), individual cardiovascular endpoints, and safety, with pooled risk ratios (RR) and mean differences calculated using random-effects models. RESULTS: Nine trials enrolling 67,662 patients were included. Evolocumab significantly reduced LDL-C (mean difference -57.73 mg/dL), total cholesterol (-52.27 mg/dL), triglycerides (-21.21 mg/dL), and lipoprotein(a) (-10.99 mg/dL), while increasing HDL-cholesterol (3.69 mg/dL). Evolocumab was associated with lower MACE (RR 0.53; 95% CI 0.40-0.71), though this estimate should be interpreted cautiously given heterogeneity in endpoint definitions and study designs. Myocardial infarction (RR 0.74) and coronary revascularisation (RR 0.80) were significantly reduced, while cardiovascular mortality and stroke showed no statistically definitive reduction. Serious adverse events and neurocognitive effects were comparable between groups, though injection-site reactions were more frequent with evolocumab. CONCLUSION: In patients with established cardiovascular disease, evolocumab provides substantial lipid lowering and reduces ischemic events without major safety concerns, supporting its use as an adjunct to statin therapy in secondary prevention.