Abstract Body (Do not enter title and authors here): Introduction:
Ischemic heart disease (IHD) remains a leading global cause of morbidity and mortality despite advances in therapies. Lowering low-density lipoprotein cholesterol (LDL-C) is critical in reducing cardiovascular risk. Statins are usually the first-line agents, but many patients either fail to reach LDL-C targets or remain at residual risk. Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors effectively lower LDL-C and provide cardiovascular benefits in high-risk patients. This meta-analysis assessed both the efficacy and safety of PCSK9 inhibitors used in conjunction with statins in patients with IHD, with a focus on efficacy and safety endpoints.
Methods:
We systematically searched PubMed, Cochrane Library, and ClinicalTrials.gov through May 2025 for randomized controlled trials (RCTs) comparing PCSK9 inhibitors plus statins vs. placebo with or without statins in patients with IHD. Three reviewers independently extracted data. Efficacy outcomes included LDL-C at 30 days; ischemic stroke; heart failure hospitalization; unstable angina; neurocognitive events; all-cause mortality; myocardial infarction (MI) and coronary revascularization. Safety outcomes included injection site and allergic reactions. Pooled risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Means and standard deviations were estimated from medians/IQRs by Wan’s method. Study quality was assessed using Cochrane RoB 2.0. Assessment of publication bias was not feasible due to fewer than 10 included studies.
Results:
In this meta-analysis, five RCTs were included. Combination therapy significantly reduced total cholesterol at 30 days (MD =–49.21 mg/dl; 95% CI; –90.68 to –7.74; p = 0.02) coronary revascularization (RR = 0.84; 95% CI: 0.76–0.93; p = 0.0008), MI (RR 0.76; 95% CI; 0.62-0.93; p= 0.007) and increased the risk of injection site reactions (RR=1.36; 95% CI: 1.16–1.59; p = 0.0001). Sensitivity analyses were conducted to address heterogeneity. No significant differences were observed for all-cause mortality, stroke, heart failure, neurocognitive events, or allergic reactions.
Conclusion:
In patients with IHD, the addition of PCSK9 inhibitors to statin therapy improved lipid levels and reduced coronary revascularization with a favorable safety profile. These findings support their use in select high-risk populations who remain inadequately managed on statins alone.