EVALUATING THE EFFICACY OF PCSK9 INHIBITORS IN ATHEROSCLEROTIC CARDIOVASCULAR DISEASE (ASCVD): A SYSTEMATIC REVIEW

Abstract

Background: Atherosclerotic cardiovascular disease (ASCVD) remains a leading global cause of morbidity and mortality. Despite intensive statin therapy, many patients fail to achieve optimal lipid control, necessitating alternative treatments. This systematic review synthesizes evidence from clinical trials evaluating the efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors—evolocumab, alirocumab, and inclisiran—in ASCVD management. Methods: Following PRISMA 2020 guidelines, a comprehensive literature search was conducted in PubMed, Scopus, Web of Science, Embase, and Google Scholar up to December 2025. Ten randomized controlled trials and phase III studies meeting inclusion criteria were analyzed. Data extracted included LDL-C reduction, major adverse cardiovascular events (MACE), and safety outcomes. Results: Across studies, PCSK9 inhibitors reduced LDL-C by 50–65% relative to baseline and significantly lowered MACE rates, including myocardial infarction and stroke. Evolocumab and alirocumab demonstrated sustained cardiovascular protection when added to maximally tolerated statin therapy. Inclisiran achieved comparable LDL-C reductions with a twice-yearly dosing schedule. Adverse events were minimal, primarily limited to mild injection-site reactions. Conclusion: PCSK9 inhibitors provide potent, durable LDL-C lowering and meaningful reductions in cardiovascular events, representing a major advancement in secondary prevention of ASCVD. Their efficacy, safety, and emerging long-term outcome data affirm their role as essential adjuncts to statins, especially in high-risk or statin-intolerant populations.