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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
Journal article   Open access   Peer reviewed

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

Dean J Kereiakes, Jennifer G Robinson, Christopher P Cannon, Christelle Lorenzato, Robert Pordy, Umesh Chaudhari and Helen M Colhoun
The American heart journal, Vol.169(6), pp.906-915.e13
06/2015
DOI: 10.1016/j.ahj.2015.03.004
PMID: 26027630
url
https://doi.org/10.1016/j.ahj.2015.03.004View
Published (Version of record) Open Access

Abstract

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. 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). 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. 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.
 Proprotein Convertases - antagonists & inhibitors Hypercholesterolemia - blood Double-Blind Method Humans Middle Aged Risk Factors Antibodies, Monoclonal - adverse effects Antibodies, Monoclonal - therapeutic use Male Hypercholesterolemia - drug therapy Cardiovascular Diseases - complications Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Antibodies - blood Cholesterol, LDL - blood Female Hypercholesterolemia - complications Serine Endopeptidases Antibodies, Monoclonal - immunology Proprotein Convertase 9

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