Abstract 4370846: Real-World Outcomes of Inclisiran vs. Ezetimibe in Statin-Treated Coronary Artery Disease Patients: A 1-Year Observational Analysis

Abstract

Background: Residual risk of adverse cardiovascular events remains high among patients with coronary artery disease (CAD) despite high-intensity statin therapy. Although ezetimibe is the standard non-statin add-on, inclisiran, a PCSK9-targeting siRNA, may confer greater reductions in mortality and major events. We compared 1-year real-world outcomes of inclisiran versus ezetimibe in patients with CAD and hyperlipidemia. Methods: In this retrospective, propensity score-matched study using the TriNetX US Collaborative Network, adults with CAD (ICD-10 I25.10) and hyperlipidemia (ICD-10 E78.5) on atorvastatin 40–80 mg plus either ezetimibe (n = 136,655 before matching) or inclisiran (n = 1205) from January 2005 to June 2025 were identified. After 1:1 matching (n = 1205 per group) for demographics, comorbidities, concomitant cardiovascular medications, and baseline LDL-C, patients were followed from day +1 to day 365 post-index. The primary endpoint was all-cause mortality; secondary endpoints were acute myocardial infarction (AMI), ischemic/hemorrhagic stroke, and LDL-C ≤ 70 mg/dL at 12 months. Kaplan-Meier curves, log-rank tests, and Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Baseline characteristics were balanced (mean age 70 ± 9 years; 44% female; median LDL-C ≈ 105 mg/dL). At 12 months, all-cause mortality was 0.8% with inclisiran versus 3.4% with ezetimibe (HR 0.14; 95% CI 0.06–0.33; p < 0.001). AMI occurred in 10.5% versus 13.3% (HR 0.74; 95% CI 0.59–0.93; p = 0.011), and stroke in 5.8% versus 7.9% (HR 0.70; 95% CI 0.51–0.96; p = 0.023). Achievement of LDL-C ≤ 70 mg/dL was similar (34.5% vs. 31.3%; HR 1.05; 95% CI 0.83–1.09; p = 0.452) as shown in table 1. Conclusions: In this large, real-world cohort of CAD patients on high-intensity statins, adding inclisiran was associated with an 85% reduction in 1-year all-cause mortality and significant reductions in AMI and stroke compared with ezetimibe, without compromising LDL-C goal attainment. Prospective randomized trials are warranted to confirm these findings.