Abstract 18484: Modest Potential Association Between Reductions in Lipoprotein(a) and Major Adverse Cardiovascular Events in the Phase 3 Trials of Alirocumab versus Control

IntroductionElevated lipoprotein(a) [Lp(a)] levels may be a causal risk factor for cardiovascular (CV) disease. Alirocumab (ALI) reduces both LDL-C and Lp(a). It is unclear if there is a CV outcomes benefit associated with lowering Lp(a) with ALI.MethodsWe assessed risk of major adverse CV events (MACECHD death, non-fatal MI, ischemic stroke, or unstable angina requiring hospitalization) with respect to both achieved and % change in Lp(a) during treatment in 10 Phase 3 ODYSSEY trials that compared ALI with ezetimibe or placebo (n=4974). Lp(a) levels were determined by a validated immunoturbidimetric assay. In multivariable models, achieved Lp(a) values were assessed following log-transformation per 1.06 loge (or 2.9-fold) decrease or per 50% reduction, with adjustment for baseline LDL-C and either average achieved LDL-C or % reduction in LDL-C, respectively.ResultsMedian (Q1-Q3) baseline Lp(a) levels were 23.5 (8-67) mg/dL. ALI provided median Lp(a) reductions from baseline of 25.6% (placebo-controlled pool) and 21.4% (ezetimibe-controlled pool). During treatment 104 patients experienced MACE (6699 patient years). In analyses unadjusted for on treatment LDL-C or % reductions in LDL-C, the Hazard Ratio (HR) for a 2.9-fold lower Lp(a) was 0.89 (95% CI 0.77 to 1.03) and 0.77 (95% CI 0.61 to 0.97) for a 50% lowering. Adjustment for LDL-C slightly attenuated this trend towards lower MACE risk with lower average achieved Lp(a) (HR [95% CI]0.91 [0.79 to 1.06] per 2.9-fold decrease; p=0.25) or with greater % Lp(a) reduction (HR [95% CI]0.84 [0.65 to 1.10] per 50% reduction; p=0.20). When stratified by baseline Lp(a) (≥50 vs