Efficacy and safety of PCSK-9 inhibitors in patients with acute coronary syndrome: a systematic review and network meta-analysis

Acute coronary syndrome (ACS) remains a leading cause of global cardiovascular morbidity and mortality, with elevated low-density lipoprotein cholesterol (LDL-C) being a key modifiable risk factor. Despite statin therapy, many patients fail to achieve optimal LDL-C targets, highlighting the need for adjunctive treatments such as PCSK9 inhibitors (e.g., Evolocumab and Alirocumab). However, comparative evidence on their efficacy and safety in ACS patients remains limited.

To systematically evaluate the efficacy and safety of PCSK9 inhibitors (Evolocumab and Alirocumab) in patients with ACS, focusing on LDL-C reduction and major adverse cardiovascular events (MACE).

A comprehensive search was conducted in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and the WHO International Clinical Trials Registry. Eligible randomized controlled trials (RCTs) assessed PCSK9 inhibitors in ACS patients and reported outcomes on LDL-C and MACE. Both direct and network meta-analyses were performed to compare effect sizes across interventions. No direct head-to-head trials between Evolocumab and Alirocumab were identified.

Nine RCTs involving 37,934 patients were included. Direct meta-analysis showed that PCSK9 inhibitors significantly reduced LDL-C (mean difference [MD]: − 52.7 mg/dL; 95% CI: − 61.2 to − 44.1) and lowered the risk of MACE (odds ratio [OR]: 0.79; 95% CI: 0.68–0.93). In subgroup analysis, Evolocumab produced greater LDL-C reductions, while Alirocumab showed a stronger trend toward MACE reduction, though not statistically significant (OR: 0.84; 95% CI: 0.68–1.03). Network meta-analysis confirmed these patterns but revealed no statistically significant differences between the two agents.

PCSK9 inhibitors significantly improve lipid profiles and reduce cardiovascular event risk in ACS patients. While Evolocumab and Alirocumab offer similar overall benefits, their differential effects on LDL-C and MACE warrant further investigation. These findings support the role of PCSK9 inhibitors in secondary prevention strategies for high-risk cardiovascular populations.