Evolocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, potently reduces low-density lipoprotein cholesterol. However, its effects on hard clinical endpoints and safety in patients with atherosclerotic cardiovascular disease (ASCVD) require updated synthesis, particularly incorporating data from recent long-term extension studies and diverse subpopulations. To systematically evaluate the efficacy and safety of evolocumab in patients with ASCVD. PubMed, Embase, Cochrane Library, OVID, China National Knowledge Infrastructure (WANFANG MED ONLINE and CNKI), and ClinicalTrials.gov were systematically searched from January 2014 to March 2026. Randomized controlled trials (RCTs) comparing evolocumab with placebo in patients with ASCVD were included. The primary endpoint was major adverse cardiovascular events (MACE). A random-effects model was used for meta-analysis, with subgroup analyses, meta-regression, sensitivity analyses, and publication bias assessment. Eight RCTs comprising 40,658 patients were included. Regarding lipid parameters, evolocumab significantly reduced levels of low-density lipoprotein cholesterol (LDL-C; standardized mean difference SMD: -2.546, 95% confidence interval CI: -3.024 to -2.067, P < 0.001), total cholesterol (TC; SMD: –1.543, 95% CI: –1.947 to –1.139, P < 0.001), apolipoprotein B (Apo B; SMD: –1.598, 95% CI: –2.169 to –1.027, P < 0.001), and lipoprotein(a) (Lp(a); SMD: –0.713, 95% CI: –0.938 to –0.489, P < 0.001) compared with placebo, but showed no significant effect on high-density lipoprotein cholesterol (HDL-C; SMD: 0.233, 95% CI: –0.058 to 0.524, P = 0.117) or triglycerides (TG; SMD: –0.315, 95% CI: –0.765 to 0.136, P = 0.171). For clinical endpoints, evolocumab significantly reduced the odds of MACE compared with placebo (OR: 0.416, 95% CI: 0.248–0.698, P < 0.001; I 2 = 86.7%); however, the 95% prediction interval crossed unity (0.13–1.36), indicating uncertainty about the true effect in future studies. Myocardial infarction (OR: 0.711, 95% CI: 0.661–0.765, P < 0.001), stroke (OR: 0.774, 95% CI: 0.693–0.864, P < 0.001), and coronary revascularization (OR: 0.777, 95% CI: 0.734–0.821, P < 0.001) all showed significant odds reductions. Evolocumab significantly reduced odds of cardiovascular death (OR: 0.771, 95% CI: 0.657–0.904, P = 0.002) and all-cause mortality (OR: 0.852, 95% CI: 0.762–0.953, P = 0.004). Safety analysis indicated that injection site reactions were more common with evolocumab (OR: 1.33, 95% CI: 1.12–1.59, P < 0.01), with no significant differences in serious adverse events, neurocognitive events, muscle-related events, or liver function abnormalities. In the context of optimized background therapy, evolocumab significantly reduces the odds of MACE, myocardial infarction, and stroke, and improves multiple atherogenic lipid parameters in patients with ASCVD. Notably, significant reductions in both cardiovascular and all-cause mortality were also observed in this updated analysis. Its overall safety profile is favorable.
Li et al. (2026) studied this question.
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