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

Frederick J. Raal, Jaakko Tuomilehto, Andrei C. Sposito, Francisco A. Fonseca, Maurizio Averna, Michel Farnier, Raul D. Santos, Keith C. Ferdinand, R. Scott Wright, Eliano Pio Navarese, Danielle M. Lerch, Michael J. Louie, L. Veronica Lee, Alexia Letierce, Jennifer G. Robinson

Research output: Contribution to journalArticle

Abstract

Background: Age, smoking, hypercholesterolemia, and hypertension are major risk factors for atherosclerotic cardiovascular disease. Objective: We examined whether the effects of alirocumab on low-density lipoprotein cholesterol (LDL-C) differed according to age, hypertension, or smoking status. Methods: Data were pooled from 10 Phase 3 ODYSSEY randomized trials (24–104 weeks’ 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 75 mg every 2 weeks (Q2W) to 150 mg Q2W at Week 12 if predefined risk-based LDL-C goals were not achieved at Week 8 (≥70 mg/dL in very high cardiovascular risk; ≥100 mg/dL in moderate or high cardiovascular risk). Two trials compared alirocumab 150 mg Q2W vs placebo. The efficacy and safety of alirocumab were assessed post hoc in subgroups stratified by age (<65, ≥65 to <75, ≥75 years) and baseline hypertension or smoking status. Results: Alirocumab reduced LDL-C by 23.7% (75/150 mg vs ezetimibe + statin) to 65.4% (150 mg 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)735-743
Number of pages9
JournalJournal of Clinical Lipidology
Volume13
Issue number5
DOIs
StatePublished - Sep 1 2019

Keywords

  • Age
  • Cholesterol
  • Hypercholesterolemia
  • Hypertension
  • PCSK9
  • Smoking

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine

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    Raal, F. J., Tuomilehto, J., Sposito, A. C., Fonseca, F. A., Averna, M., Farnier, M., Santos, R. D., Ferdinand, K. C., Wright, R. S., Navarese, E. P., Lerch, D. M., Louie, M. J., Lee, L. V., Letierce, A., & Robinson, J. G. (2019). Treatment effect of alirocumab according to age group, smoking status, and hypertension: Pooled analysis from 10 randomized ODYSSEY studies. Journal of Clinical Lipidology, 13(5), 735-743. https://doi.org/10.1016/j.jacl.2019.06.006