LONG-TERM CARDIOVASCULAR OUTCOMES AND SAFETY PROFILE OF PCSK9 INHIBITORS IN HIGH-RISK POPULATIONS FOR SECONDARY PREVENTION OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASE: A COMPREHENSIVE META-ANALYSIS OF MORTALITY, MAJOR ADVERSE CARDIAC EVENTS, AND METABO

Background: Cardiovascular disease (CVD) is the principal cause of mortality globally, especially among individuals at high risk. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors, innovative lipid-lowering medications, have shown promise in substantially lowering low-density lipoprotein cholesterol (LDL-C) and reducing cardiovascular risks. Objective: This study aims to evaluate the long-term cardiovascular outcomes and safety profile of PCSK9 inhibitors in high-risk populations with established atherosclerotic cardiovascular disease (ASCVD), focusing on their effects on mortality, major adverse cardiac events (MACE), and metabolic markers. Methods: Adhering to PRISMA guidelines, a detailed literature review was conducted across PubMed, Scopus, and Google Scholar. The search included randomized controlled trials (RCTs) and observational studies assessing the impact of PCSK9 inhibitors in high-risk ASCVD patients. Outcomes such as mortality, MACE, and metabolic changes were examined. Data were analyzed using random-effects models to accommodate heterogeneity. Results: The analysis included ten studies comprising patients with high-risk ASCVD, revealing that PCSK9 inhibitors led to a 15% reduction in the incidence of cardiovascular events (pooled effect size: 0.85, 95% CI: 0.78-0.91, p < 0.001). Additionally, there was a significant decrease in LDL-C levels (effect size: 0.87, 95% CI: 0.82-0.93, p < 0.001) and post-acute coronary syndrome (ACS) mortality (effect size: 0.90, 95% CI: 0.84-0.96, p = 0.02). Subgroup analyses further highlighted the pronounced benefits for older adults and individuals with diabetes. Conclusion: PCSK9 inhibitors significantly reduce cardiovascular events, MACE, and mortality in high-risk ASCVD patients, emphasizing their critical role in secondary prevention strategies for CVD, particularly in those with elevated LDL-C and increased cardiovascular risk.