EFFICACY OF PCSK9 INHIBITORS IN REDUCING MAJOR CARDIOVASCULAR EVENTS IN PATIENTS

Introduction: Proprotein convertase subtilisin/kexin type 9 inhibitors have emerged as a major pharmacological advance in lipid-lowering therapy, particularly for patients at high and very high cardiovascular risk who do not achieve adequate low-density lipoprotein cholesterol reduction with statins alone. Despite robust lipid-lowering effects, the magnitude and consistency of their impact on major adverse cardiovascular events across different populations and clinical contexts remain an area of active investigation. Objective: The main objective of this systematic review is to evaluate the efficacy of PCSK9 inhibitors in reducing major cardiovascular events in adult patients at increased cardiovascular risk. Secondary objectives include assessing effects on individual cardiovascular outcomes, exploring differences according to baseline risk and concomitant therapies, evaluating safety and tolerability profiles, analyzing consistency across randomized and observational designs, and identifying gaps in current evidence to guide future research. Methods: A systematic search was planned across PubMed, Scopus, Web of Science, the Cochrane Library, LILACS, ClinicalTrials.gov, and the International Clinical Trials Registry Platform. Eligible studies include randomized controlled trials and observational studies published within the last five years, with possible extension to ten years if fewer than ten studies meet eligibility criteria. Data synthesis is planned using qualitative comparative analysis, with risk of bias assessed using validated tools and certainty of evidence graded according to GRADE methodology. Results and Discussion: The final synthesis will include all eligible studies that evaluated PCSK9 inhibitors in relation to major cardiovascular outcomes, such as myocardial infarction, stroke, cardiovascular mortality, and composite endpoints. Results will be discussed in the context of study design, population characteristics, baseline lipid levels, and concurrent lipid-lowering strategies, with attention to heterogeneity and alignment with contemporary cardiovascular prevention guidelines. Conclusion: This systematic review aims to provide a comprehensive, practice-oriented evaluation of the role of PCSK9 inhibitors in cardiovascular risk reduction, supporting evidence-based decision-making in lipid management for high-risk patient populations.