Elsevier

American Heart Journal

Volume 169, Issue 6, June 2015, Pages 906-915.e13
American Heart Journal

Clinical Investigation
Prevention and Rehabilitation
Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO I study

https://doi.org/10.1016/j.ahj.2015.03.004Get rights and content
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open access

Background

The ODYSSEY COMBO I study (http://clinicaltrials.gov/show/NCT01644175) evaluated efficacy and safety of alirocumab as add-on therapy to stable maximally tolerated daily statin with or without other lipid-lowering therapy in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia.

Methods

This multicenter, phase 3, randomized (2:1 alirocumab vs placebo), double-blind, 52-week trial enrolled 316 patients with established coronary heart disease or coronary heart disease risk equivalents and hypercholesterolemia. Alirocumab (75 mg every 2 weeks [Q2W]) or placebo Q2W was self-administered subcutaneously via 1 mL prefilled pen. The alirocumab dose was increased to 150 mg Q2W (also 1 mL) at week 12 if week 8 low-density lipoprotein cholesterol (LDL-C) was ≥70 mg/dL. The primary efficacy end point was percent change in LDL-C from baseline to week 24 (intention-to-treat analysis).

Results

At week 24, estimated mean (95% CI) changes in LDL-C from baseline were −48.2% (−52.0% to −44.4%) and −2.3% (−7.6% to 3.1%) for alirocumab and placebo, respectively, an estimated mean (95% CI) difference of −45.9% (−52.5% to −39.3%) (P < .0001). Low-density lipoprotein cholesterol <70 mg/dL was achieved by 75% alirocumab versus 9% placebo patients at week 24. At week 12, 83.2% of evaluable alirocumab-treated patients remained on 75-mg Q2W. Treatment-emergent adverse events were comparable between groups.

Conclusions

Alirocumab treatment achieved a significantly greater reduction in LDL-C and allowed a greater proportion of patients to achieve LDL-C goals, versus placebo after 24 weeks in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia at baseline despite receiving maximally tolerated statin with or without other lipid-lowering therapy. The frequency of treatment-emergent adverse events and study medication discontinuations were generally comparable between treatment groups.

Cited by (0)

Randomized controlled trial number NCT01644175.

Disclosures: Dr Kereiakes has been a consultant or on an advisory panel for HCRI; Ablative Solution, Inc; Boston Scientific; Abbott Vascular; and REVA Medical Inc. Dr Robinson is employed by a university that has received research funds from Amarin, Amgen, AstraZeneca, Daiichi-Sankyo, Esai, GlaxoSmithKline, Merck, Regeneron/Sanofi, and Zinfandel/Takeda; and is a consultant for Amgen, Pfizer, Sanofi, and Regeneron. Dr Cannon has received grants from Accumetrics, Arisaph, AstraZeneca, Boehringer-Ingelheim, Janssen; grants and personal fees from GlaxoSmithKline, Merck, and Takeda; and consulting fees from BMS, CSL Behring, Essentialis, Lipimedix, Pfizer, Regeneron, and Sanofi. Ms Lorenzato and Dr Chaudhari are employees and stockholders of Sanofi. Dr Pordy is an employee and stockholder of Regeneron Pharmaceuticals, Inc. Dr Colhoun is a consultant or on an advisory panel for Pfizer, Sanofi Aventis, Regeneron, Novartis, and Eli Lilly; has received research support from Roche, Pfizer, Eli Lilly, Boehringer Ingelheim, AstraZeneca; has participated in a lecture/speaker's bureau and received honorarium from Pfizer; and is a shareholder in Roche.

Author contributions: D. Kereiakes wrote the first draft and was involved in data collection, analysis, and interpretation. J. Robinson, C. Cannon, C. Lorenzato, R. Pordy, U. Chaudhari, and H. Colhoun were involved in revising the manuscript; and all were involved in the study design, data analysis, and interpretation. All authors provided final approval to submit the manuscript.