PCSK-9 Inhibitors and Cardiovascular Outcomes: A Systematic Review With Meta-Analysis

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been approved to treat dyslipidaemia. However, there is a lack of knowledge on the most efficient PCSK9 therapies that target PCSK9 for secondary prevention in subjects at high risk for cardiovascular (CV) events. Thus, this study aimed to assess the efficacy and safety of anti-PCSK9 antibodies in randomized controlled trials (RCTs). A comprehensive review of the available literature was done to identify RCTs that compared the use of PCSK9 inhibitors coupled with placebo or ezetimibe for the secondary prevention of CV events in patients on statin-background therapy. All-cause mortality was the major efficacy endpoint, while severe adverse events were the key safety outcome. A random effects model was used, and data were presented as risk ratio (RR) or risk difference with their corresponding 95% confidence intervals (CI). The heterogeneity of the publications was determined using Cochran's Q test, and publication bias was visually examined using funnel plots. All the chosen studies' quality was assessed using the Critical Appraisal Checklists for Studies created by the Joanna Briggs Institute (JBI). Forty-one studies (76,304 patients: 49,086 on evolocumab, and 27,218 on alirocumab) were included, and their years of publication spanned from 2010 to 2023. Overall, no significant differences were observed in CV and all-cause mortality between PCSK9 inhibitors and controls. However, alirocumab use was linked to a reduced risk of all-cause death compared to control, but not evolocumab. Each of the drugs, evolocumab and alirocumab, significantly reduced the risk of myocardial infarction (MI), coronary revascularization, and ischemic stroke. In comparison to the control therapy, the risk of major detrimental sequelae was significantly reduced by alirocumab therapy in the subgroup analysis of each PCSK9 inhibitor, whereas evolocumab treatment did not demonstrate significant differences (RR = 0.88; 95% CI = 0.72-1.04; evolocumab: RR = 0.99; 95% CI = 0.87-1.11). Both evolocumab and alirocumab are well-tolerated, safe medications that significantly lower low-density lipoprotein (LDL) levels.