AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Association of PCSK9 Inhibitor Use with Clinical Outcomes in Patients with Aortic Stenosis: A Retrospective Electronic Health Record-Based Analysis
By Sharma S, Ali M, Jamil R et al.
Background: PCSK9 inhibitors (PCSK9i) are monoclonal antibodies that substantially lower LDL-C and modestly reduce lipoprotein(a) [Lp(a)]. They represent an emerging cornerstone in ASCVD risk reduction. There is a strong association between calcific aortic stenosis and elevated LDL-C and Lp(a) levels. Existing evidence supporting the use of PCSK9i, such as the post hoc analysis of the FOURIER trial, did not yield conclusive results in this regard due to the low event rate of new or worsening AS. This study aims to evaluate the clinical outcomes of PCSK9 inhibitor use in patients with aortic stenosis. Methods: This analysis used the TriNetX Global Collaborative Network. Cohort 1 included patients with hyperlipidemia and aortic stenosis who were prescribed evolocumab, alirocumab, or inclisiran. Cohort 2 consisted of patients with hyperlipidemia and aortic stenosis who did not have these PCSK9 inhibitor medications prescribed. Both groups excluded patients with prior TAVR or TAVI and a heart failure diagnosis. Propensity score matching was used. After matching, there were 5,975 patients per group, and most baseline variables were well balanced. Outcomes included all-cause mortality, STEMI, stroke, atrial fibrillation, ER visit or hospitalization, and ventricular tachycardia or ventricular fibrillation (VT/VF). Results: PCSK9i use was associated with lower all-cause mortality (HR 0.386, 95% CI 0.334-0.446; log-rank p < 0.001) and fewer ER visits or hospitalizations (HR 0.800, 95% CI 0.758-0.845; log-rank p < 0.001). Risk analyses also showed lower rates of STEMI (RR 0.772, 95% CI 0.640-0.931), stroke (RR 0.730, 95% CI 0.611-0.872), atrial fibrillation (RR 0.653, 95% CI 0.569-0.751), and VT/VF (RR 0.811, 95% CI 0.737-0.892), although corresponding Kaplan-Meier analyses for these outcomes were not statistically significant. Conclusion: In a large propensity-matched EHR-based analysis of patients with aortic stenosis and hyperlipidemia, PCSK9 inhibitor use was associated with significantly lower all-cause mortality and reduced rates of ER visits or hospitalization. These findings suggest a potential clinical benefit of intensive lipid-lowering therapy in this high-risk population and warrant further prospective studies.