AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Efficacy of Proprotein Convertase Subtilisin Kexin Type 9 Inhibitor versus Statin Monotherapy in Patients with Elevated Lipoprotein(a): A Target Trial Emulation
By Babapour G, Chowdhury I, Chang Y et al.
Background: Elevated lipoprotein(a) [Lp(a)] is associated with residual atherosclerotic cardiovascular disease (ASCVD) risk despite lipid-lowering therapy. High-intensity statins effectively reduce LDL-C; they may modestly increase Lp(a). In contrast, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) reduce both LDL-C and Lp(a), although comparative outcome data in patients with elevated Lp(a) remain limited. Research Question: Among patients with elevated baseline Lp(a), is initiation of PCSK9i monotherapy, compared with high-intensity statin monotherapy, associated with lower risk of major adverse cardiovascular events (MACE)? Methods: We conducted a retrospective cohort study using a target-trial emulation framework using the TriNetX Global Collaborative Network, including adults with hyperlipidemia and elevated Lp(a) (≥75 nmol/L or ≥30 mg/dL) from January 2015 to December 2025. Patients initiating PCSK9i monotherapy meeting eligibility criteria (Time 0) were compared with those initiating high-intensity statin monotherapy during the same window, using an intention-to-treat framework. Propensity score matching (1:1) was used to balance standardized mean differences to <0.1 across demographics, comorbidities, laboratory values, cardiovascular risk factors, and baseline medications. The primary outcome was MACE (all-cause mortality, myocardial infarction, stroke, TIA). Secondary outcomes included major adverse limb events (MALE), acute myocardial infarction, the composite of stroke, TIA, or intracranial hemorrhage (ICH), coronary revascularization, peripheral revascularization, all-cause mortality, and ICH as a standalone outcome. Follow-up began at Time 0 up to 1 year. Cox proportional hazards models were used to estimate HRs and 95% CIs. Results: Among 10,934 eligible patients, 4,146 propensity score–matched patients were included (2,073 per group; mean age 61.5±11.4 years; 53.1% women). Median follow-up was 365 days in both cohorts. MACE occurred less frequently with PCSK9i monotherapy compared with high-intensity statin monotherapy at 1 year (8.3% vs. 12.2%; HR 0.76, 95% CI 0.63–0.92; p=0.005). PCSK9i monotherapy was also associated with significantly lower rates of MALE (0.8% vs. 1.9%; HR 0.48, 95% CI 0.27–0.84; p=0.009). Acute myocardial infarction (HR 0.77, 95% CI 0.59–1.02; p=0.065) and the composite of stroke, TIA, or ICH (HR 0.80, 95% CI 0.61–1.04; p=0.093) numerically favored PCSK9i without statistical significance. The falsification endpoint of gastritis did not differ between groups (HR 1.14; p=0.569). Conclusions: In patients with elevated Lp(a), PCSK9i monotherapy was associated with lower rates of MACE and MALE compared with high-intensity statin monotherapy at 1-year follow-up, suggesting a potential strategy to reduce residual ASCVD risk in this high-risk population.