Abstract 4363298: Real-World Outcomes of Adding PCSK9 Inhibitors to High-Intensity Statin Therapy Following Acute Coronary Syndrome: A Nationwide Cohort Study

Abstract

Background: PCSK9 inhibitors reduce cardiovascular risk in high-risk populations, yet real-world data evaluating their additive benefit following acute coronary syndrome (ACS) are limited. While randomized trials have demonstrated efficacy, the optimal timing of PCSK9 inhibitor initiation post-ACS remains unclear. Notably, no large-scale real-world studies have evaluated the impact of early addition of PCSK9 inhibitors to high-intensity statin therapy following ACS. Objective: To assess the 1-year major cardiovascular events (MACE) among ACS patients treated with high-intensity statins plus PCSK9 inhibitors vs high-intensity statins alone. Methods: Using the TriNetX Research Network of 103 healthcare organizations, we identified adults (≥18 years) hospitalized with ACS between 2015 and 2023 who underwent percutaneous coronary intervention and initiated high-intensity statin therapy. Among 182,176 eligible patients, 2,311 received a PCSK9 inhibitor (alirocumab or evolocumab) within 90 days of discharge and were propensity score matched 1:1 to 2,311 patients who received statins alone. The primary outcome was a composite of all-cause mortality, recurrent myocardial infarction (MI), and stroke at 1 year. Secondary outcomes included individual components and all-cause rehospitalization. Results: At 1 year, the primary outcome occurred in 8.5% of the PCSK9i group versus 10.4% in the non-PCSK9i group (RR, 0.82; 95% CI, 0.71–0.95; HR, 0.82; 95% CI, 0.70–0.96; p = 0.014). All-cause mortality was lower in the PCSK9i group (3.1% vs. 4.7%, RR 0.66, 95% CI 0.51–0.87, HR 0.66, 95% CI 0.50–0.86; p=0.002). Recurrent MI (3.4% vs. 4.2%, RR 0.80, 95% CI 0.62–1.03, HR 0.80, 95% CI 0.61–1.04; p=0.09) and stroke (1.6% vs. 2.3%, RR 0.71, 95% CI 0.47–1.06, HR 0.71, 95% CI 0.46–1.10; p=0.13) were not statistically significant. Rehospitalization was lower in the PCSK9i group (9.3% vs. 11.8%, RR 0.79, 95% CI 0.68–0.93, HR 0.79, 95% CI 0.67–0.93; p=0.006). Similar trends were observed at 6 months, with lower primary outcome (6.0% vs. 7.3%, HR 0.81, 95% CI 0.67–0.99; p=0.038), all-cause mortality (2.0% vs. 3.0%, HR 0.65, 95% CI 0.47–0.90; p=0.009). Conclusion: In this large, real-world cohort, the addition of PCSK9 inhibitors to high-intensity statins following ACS was associated with significantly lower MACE. These findings support the real-world effectiveness of their early initiation in high-risk secondary prevention.