Abstract
Background: Coronary artery disease (CAD), manifested mainly as acute coronary syndrome (ACS), continues to be a major cause of mortality globally and a significant contributing factor to the global disease burden. Elevation of low-density lipoprotein cholesterol levels attributed to proprotein convertase subtilisin/Kexin type-9 (PCSK9) during and following ACS puts patients at high risk of subsequent adverse events. Evolocumab is a PCSK9 inhibitor that is associated with a significant reduction in low-density lipoprotein cholesterol (LDL-C) levels through PCSK9 inhibition in comparison to traditional statin therapy.
Methods: We conducted a systematic review and meta-analysis of literature addressing the efficacy and safety of evolocumab compared to other lipid-lowering therapies or placebo. An extensive internet-based literature search using pre-determined key phrases supported by medical sub-headings and Boolean operators was performed in October 2022 to identify literature pertinent to the research topic. The search was primarily based on the National Library of Medicine (PubMed and Clinical Trials), MEDLINE, Cochrane, and the Science direct literature databases. Subsequently, the researchers devised PICOs-based screening criteria which had to be met by each identified study for inclusion in the review and meta-analysis. Two independent reviewers conducted data stratification and quality assessment of identified studies. Statistical analysis of the primary and secondary outcomes was conducted on the Cochrane REVMAN 5.4 statistical software for randomized trials.
Results: Two thousand five hundred and seventy-six potential studies were identified for inclusion in the systematic review. Data stratification, screening, and quality assessment of these studies based on the eligibility criteria led to the exclusion of two thousand five hundred and sixty-seven studies as they did not meet the standards set. Nine randomized controlled trials progressed to numerical analysis for validity and reliability. Eight studies were included in the meta-analysis. Meta-analytical results showed a significant decrease in LDL-C changes from initiation of evolocumab therapy to 8 weeks following ACS compared to placebo. Similar results were derived in the sub-acute phase of ACS [SMD -1.95 (95% CI -2.29, -1.62)]. The meta-analysis revealed no statistically significant relationship between the risk of adverse effects, serious adverse effects, and major adverse cardiovascular events (MACE) from treatment using evolocumab in comparison to placebo [(relative risk, RR 1.04 (95% CI 0.99, 1.08) (Z = 1.53; p=0.12)].
Conclusion: Early evolocumab therapy initiation was associated with a significant decrease in LDL-C levels and was not associated with an increased risk of adverse effects in comparison to placebo.