ODYSSEY COMBO II | Clinical Trial - ODYSSEY COMBO II

Feb 16, 2015
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Trial Sponsor:
Sanofi, Regeneron
Date Presented:
08/31/2014
Date Published:
02/16/2015
Date Updated:
02/16/2015
Original Posted Date:
08/31/2014
References

Description:

The goal of the trial was to evaluate treatment with alirocumab, a monoclonal antibody targeting PCSK9, compared with ezetimibe among participants with high cardiovascular risk on maximum tolerated statin therapy.

Contribution to the Literature: This trial showed that among patients with high cardiovascular risk treated with statin therapy, alirocumab resulted in a large reduction in LDL-C.

Study Design

  • Placebo Controlled
  • Randomized
  • Blinded
  • Parallel

Patient Populations:

  • Participants with high cardiovascular risk
  • On maximum tolerated statin therapy
  • Low-density lipoprotein cholesterol (LDL-C) >70 mg/dl with history of cardiovascular disease, or
  • LDL-C >100 mg/dl with no history of cardiovascular disease

    Number of enrollees: 720
    Duration of follow-up: 52 weeks
    Mean patient age: 62 years
    Percentage female: 25%

Primary Endpoints:

  • From baseline to 24 weeks, the change in LDL-C

Drug/Procedures Used:

Participants with high cardiovascular risk on maximum tolerated statin therapy were randomized to self-administered alirocumab 75 mg subcutaneous injection every 2 weeks (up-titration to 150 mg every 2 weeks), plus placebo ezetimibe (n = 479) versus placebo subcutaneous injection every 2 weeks, plus ezetimibe 10 mg daily (n = 241).

Concomitant Medications:

Statin: 99.8% (66.8% was high-intensity statin)

Principal Findings:

Overall, 720 patients were randomized. The median age was 62 years, 25% were women, mean body mass index was 30 kg/m2, and 30% had diabetes. The mean LDL-C was 109 mg/dl. The dose of alirocumab was up-titrated in 18.4% of participants.

From baseline to 24 weeks, the change in LDL-C was -50.6% for alirocumab compared with -20.7% for ezetimibe (p < 0.0001). This reduction was maintained to 52 weeks; LDL-C 53 mg/dl with alirocumab vs. 85 mg/dl with ezetimibe.

Treatment-emergent adverse events leading to drug discontinuation occurred in 7.5% of the alirocumab group vs. 5.4% of the placebo group.

Cardiovascular events occurred in 4.8% of the alirocumab group vs. 3.7% of the placebo group.

Interpretation:

Among patients with high cardiovascular risk, alirocumab resulted in a large reduction in LDL-C compared with ezetimibe, which was maintained to 52 weeks. The majority of participants were able to achieve their LDL-C target on the lower dose of alirocumab. Alirocumab appeared to be generally well-tolerated and was associated with low cardiovascular events. Future studies will examine the impact of this agent on clinical outcomes.

References:

Cannon CP, Cariou B, Blom D, et al., on behalf of the ODYSSEY COMBO II Investigators. Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial. Eur Heart J 2015;Feb 16:[Epub ahead of print].

Presented by Dr. Christopher Cannon at the European Society of Cardiology Congress, Barcelona, Spain, August 31, 2014.

Keywords: Lipoproteins, LDL, Body Mass Index, Cholesterol, LDL, Azetidines, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Injections, Subcutaneous, Risk Factors, Diabetes Mellitus, ESC Congress


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