Treatment effect of alirocumab according to age group, smoking status, and hypertension: Pooled analysis from 10 randomized ODYSSEY studies

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Age, smoking, hypercholesterolemia, and hypertension are major risk factors for atherosclerotic cardiovascular disease. We examined whether the effects of alirocumab on low-density lipoprotein cholesterol (LDL-C) differed according to age, hypertension, or smoking status. Data were pooled from 10 Phase 3 ODYSSEY randomized trials (24-104weeks' duration) in 4983 people with heterozygous familial hypercholesterolemia (FH) or non-familial hypercholesterolemia (3188 on alirocumab, 1795 on control [620 on ezetimibe and 1175 on placebo]). Most participants received concomitant maximum tolerated statin therapy. In 8 trials, the alirocumab dose was increased from 75mg every 2weeks (Q2W) to 150mg Q2W at Week 12 if predefined risk-based LDL-C goals were not achieved at Week 8 (≥70mg/dL in very high cardiovascular risk; ≥100mg/dL in moderate or high cardiovascular risk). Two trials compared alirocumab 150mg Q2W vs placebo. The efficacy and safety of alirocumab were assessed post hoc in subgroups stratified by age (<65, ≥65 to <75, ≥75years) and baseline hypertension or smoking status. Alirocumab reduced LDL-C by 23.7% (75/150mg vs ezetimibe+statin) to 65.4% (150mg vs placebo+statin) from baseline to Week 24 vs control. Subgroup analyses confirmed no significant interactions in response to alirocumab between age group, hypertension, or smoking status. Overall rates of treatment-emergent adverse events were similar between alirocumab and control groups. In this pooled analysis from 10 trials, alirocumab led to substantial LDL-C reductions vs control in every age group and regardless of hypertension or smoking status. Alirocumab was well tolerated in all subgroups.