Abstract 13567: Comparison of Change in Lipoprotein(a) Mass and Molar Concentrations by Alirocumab and Risk of Subsequent Cardiovascular Events in ODYSSEY OUTCOMES

Abstract

Background: Baseline (BL) lipoprotein(a) (Lp(a)) concentration is similarly related to cardiovascular (CV) risk when measured in either mass or molar units by immunoassay (IA). Because of Lp(a) isoform variation in mass, differences may exist between Lp(a) measurement methods in terms of relating change to risk reduction. We determined whether the reduction in major adverse cardiovascular events (MACE) by PCSK9 inhibitor alirocumab (ALI) had a similar relationship to the reduction in Lp(a) concentration as measured by 3 different methods. Methods: Lp(a) was measured by IA-mass (Siemens), IA-molar (Roche), and mass spectrometry (MS)-molar assays at BL and month 4 (M4) in a subgroup of patients in the ODYSSEY OUTCOMES trial which compared PCSK9 inhibitor ALI with placebo in patients with recent acute coronary syndrome. Changes in Lp(a) from BL to M4 were related to subsequent risk of MACE (coronary heart disease (CHD) death, nonfatal myocardial infarction (NFMI), fatal + nonfatal ischemic stroke, or unstable angina hospitalization) in the ALI group. Proportional hazards models were adjusted for BL Lp(a), BL LDL-C and its change from BL to M4, and other patient characteristics. Hazard ratios (HR) were calculated for the median change of each Lp(a) assay. All analyses were by intention-to-treat. Results: Among 5500 patients randomized to ALI with available data from all 3 Lp(a) assays, 443 experienced a subsequent MACE. Changes in Lp(a) IA-mass and MS-molar concentration were significantly related to reduced MACE risk, while change in IA-molar concentration was marginally significant; associations were more evident with CHD death + NFMI ( Figure ). MACE HRs for median change were similar across tests. Conclusion: With caveats of a modest number of MACE for analysis, moderately elevated Lp(a) levels, and intra-patient variability in serial values, 3 Lp(a) assay methods appeared similarly predictive of ALI MACE reduction.