Efficacy of PCSK9 inhibitors combined with statins versus statin monotherapy for secondary cardiovascular prevention: a systematic review and meta-analysis

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, when combined with statins, substantially reduce low-density lipoprotein cholesterol (LDL-C) in patients with established atherosclerotic cardiovascular disease (ASCVD). However, their clinical impact on major adverse cardiovascular events beyond lipid-lowering effects remains incompletely characterised. Purpose This meta-analysis aimed to compare the efficacy of PCSK9 inhibitors plus statins versus statin monotherapy in reducing cardiovascular events for secondary prevention. Methods A systematic search of PubMed, Embase, and Cochrane was conducted for randomised controlled trials (RCTs) comparing PCSK9 inhibitors (alirocumab or evolocumab) plus statins to statins alone in patients with prior ASCVD. Outcomes of interest included myocardial infarction (MI), stroke, cardiac death, and all-cause mortality. A random-effects model was used to pool data, with heterogeneity assessed using I² statistics. Results Six RCTs comprising 47,459 participants were analysed. PCSK9 inhibitors combined with statins significantly reduced the risk of MI (OR 0.79, 95% CI 0.65–0.97, p = 0.03) and stroke (OR 0.77, 95% CI 0.65–0.91, p = 0.01) compared to statins alone. No significant differences were observed for cardiac death (OR 0.97, 95% CI 0.77–1.21, p= 0.70) or all-cause mortality (OR 0.95, 95% CI 0.74–1.21, p = 0.59). Conclusion In patients with ASCVD, adding PCSK9 inhibitors to statins significantly reduces the risk of MI and stroke but does not lower mortality. These findings support their role as a complementary strategy in secondary cardiovascular prevention. Further research should investigate long-term outcomes, cost-effectiveness, and synergistic effects with novel therapies, as well as their potential role in primary prevention.