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
Key result
Alirocumab cuts LDL-C by ~46% vs placebo in high CV risk patients.
- mean difference -45.9%
- 95% CI -52.5% to -39.3%
- P<.0001
- n=316
Why the study?
Does alirocumab reduce LDL-C in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia on maximally tolerated statin therapy?
Population
316 patients with established coronary heart disease or coronary heart disease risk equivalents and…
Comparison
Alirocumab 75 mg every 2 weeks self-administered… vs Placebo Q2W self-administered subcutaneously via…
Design
RCT, 2:1 alirocumab vs placebo, double-blind
Follow-up
52 weeks
Authors
Discussion
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Implication
Supports alirocumab addition to statins in high-risk patients with uncontrolled hypercholesterolemia; confirms efficacy in this RCT population.
Key Points
- To evaluate the efficacy and safety of alirocumab as add-on therapy in high cardiovascular risk patients with uncontrolled hypercholesterolemia despite maximally tolerated statin therapy.
- Multicenter, phase 3, double-blind randomized trial (N=316; NCT01644175) allocating patients 2:1 to subcutaneous alirocumab (75 mg every 2 weeks, with potential uptitration to 150 mg at week 12 if week 8 LDL-C was ≥70 mg/dL) or placebo for 52 weeks.
- Enrolled patients with established coronary heart disease or risk equivalents and hypercholesterolemia on stable, maximally tolerated daily statins with or without other lipid-lowering therapies.
- At week 24, alirocumab reduced LDL-C from baseline by an estimated mean of -48.2% (95% CI, -52.0% to -44.4%) versus -2.3% (95% CI, -7.6% to 3.1%) with placebo, yielding an estimated mean difference of -45.9% (95% CI, -52.5% to -39.3%; P < .0001).
- LDL-C levels <70 mg/dL were achieved by 75% of alirocumab patients compared with 9% of placebo patients at week 24, with 83.2% of evaluable patients maintained on the 75 mg dose at week 12.
- Rates of treatment-emergent adverse events and study drug discontinuations were comparable between the alirocumab and placebo groups.
Study Design
Type
RCT (n=316)
Blinding
Double-blind
Randomization
2:1
Multicenter
Yes
Structured PICO
Does alirocumab reduce LDL-C in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia on maximally tolerated statin therapy?
P
Population
316 patients with established coronary heart disease or coronary heart disease risk equivalents and hypercholesterolemia, suboptimally controlled despite stable maximally tolerated daily statin with or without other lipid-lowering therapy.
I
Intervention
Alirocumab 75 mg every 2 weeks (Q2W) self-administered subcutaneously via 1 mL prefilled pen, increased to 150 mg Q2W at week 12 if week 8 LDL-C was ≥70 mg/dL, added to stable maximally tolerated daily statin with or without other lipid-lowering therapy.
C
Comparator
Placebo Q2W self-administered subcutaneously via 1 mL prefilled pen, added to stable maximally tolerated daily statin with or without other lipid-lowering therapy.
O
Outcome
Percent change in LDL-C from baseline to week 24 (intention-to-treat analysis)surrogate
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
Alirocumab added to maximally tolerated statin therapy significantly reduces LDL-C in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia.
Cite This Study
Kereiakes et al. (2015) conducted an RCT in High cardiovascular risk with suboptimally controlled hypercholesterolemia (n=316). Alirocumab vs. Placebo was evaluated on Percent change in LDL-C from baseline to week 24 (mean difference -45.9%, 95% CI -52.5% to -39.3%, p=< .0001). 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.