What is the clinical evidence from this study?

Study design: RCT. Population: High cardiovascular risk with suboptimally controlled hypercholesterolemia (n=316). Intervention: Alirocumab vs. Placebo. Primary outcome: Percent change in LDL-C from baseline to week 24 (mean difference -45.9%, 95% CI -52.5% to -39.3%, p=< .0001).

March 12, 2015Open Access

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

Q: What are the key findings of this study?

Alirocumab significantly reduced LDL-C from baseline to week 24 compared to placebo (mean difference -45.9%; 95% CI -52.5% to -39.3%; P < .0001) in high cardiovascular risk patients.

Key Result

Alirocumab significantly reduced LDL-C from baseline to week 24 compared to placebo (mean difference -45.9%; 95% CI -52.5% to -39.3%; P < .0001) in high cardiovascular risk patients.

Study Design

Type

RCT (n=316)

Blinding

Double-blind

Randomization

2:1

Multicenter

Yes

PICO

Population

High cardiovascular risk with suboptimally controlled hypercholesterolemia (n=316)

Intervention / Comparator

Alirocumab vs Placebo (75 mg every 2 weeks (Q2W), increased to 150 mg Q2W at week 12 if week 8 LDL-C ≥70 mg/dL)

Primary Outcome

Percent change in LDL-C from baseline to week 24 — mean difference -45.9% (-52.5% to -39.3%), p=< .0001

Main Result

Effect estimate: mean difference -45.9% (95% CI -52.5% to -39.3%)

Absolute Event Rate: -48.2% vs -2.3%

p-value: p=< .0001

Abstract

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.