Lipid-efficacy RCT · J Clin Lipidol 2015
ODYSSEY ALTERNATIVE trial
Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: The ODYSSEY ALTERNATIVE randomized trial.
The bottom line
In statin-intolerant patients, alirocumab lowered LDL-C far more than ezetimibe and caused fewer muscle-related adverse events than statin rechallenge with atorvastatin.
Primary lipid endpoint metUS status: US-approved
At a glance
- Medicine
- Alirocumab 75 mg SC every 2 weeks (plus oral placebo), with dose increase to 150 mg Q2W at week 12 depending on week 8 LDL-C values
- Compared with
- Ezetimibe 10 mg/d (plus SC placebo Q2W); atorvastatin 20 mg/d rechallenge arm (plus SC placebo Q2W)
- People
- 361
- Who took part
- Patients at moderate to high cardiovascular risk with statin intolerance (unable to tolerate ≥2 statins, including one at the lowest approved starting dose) due to muscle symptoms
- Design
- Randomized, single-blind placebo run-in followed by double-blind, active-comparator, 2:2:1 randomized trial with statin rechallenge arm
- Follow-up
- 24 weeks
- Main question
- Percent change in LDL-C from baseline to week 24 (intent-to-treat), alirocumab vs ezetimibe
Main result
Alirocumab reduced mean (standard error) LDL-C by 45.0% (2.2%) vs 14.6% (2.2%) with ezetimibe (mean difference 30.4% [3.1%], P < .0001)
Effect on LDL cholesterol
Baseline mean (SD) LDL-C 191.3 (69.3) mg/dL (5.0 [1.8] mmol/L); alirocumab -45.0% (2.2%) vs ezetimibe -14.6% (2.2%), mean difference 30.4% (3.1%), P<.0001
Other results
Skeletal muscle-related events were less frequent with alirocumab vs atorvastatin (hazard ratio 0.61, 95% confidence interval 0.38-0.99, P = .042)
Safety
Skeletal muscle-related events less frequent with alirocumab vs atorvastatin rechallenge (HR 0.61, 95% CI 0.38-0.99, P=.042)
In the trial's own words
“Alirocumab reduced mean (standard error) LDL-C by 45.0% (2.2%) vs 14.6% (2.2%) with ezetimibe (mean difference 30.4% [3.1%], P < .0001). Skeletal muscle-related events were less frequent with alirocumab vs atorvastatin (hazard ratio 0.61, 95% confidence interval 0.38-0.99, P = .042).”
Quoted from the abstract of J Clin Lipidol 2015, checked word for word against PubMed. PubMed 26687696 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Evolocumab (Repatha) and alirocumab (Praluent)
Common questions
What did the ODYSSEY ALTERNATIVE trial find?
In statin-intolerant patients, alirocumab lowered LDL-C far more than ezetimibe and caused fewer muscle-related adverse events than statin rechallenge with atorvastatin.
Who was in ODYSSEY ALTERNATIVE?
361 people. Patients at moderate to high cardiovascular risk with statin intolerance (unable to tolerate ≥2 statins, including one at the lowest approved starting dose) due to muscle symptoms.
What was ODYSSEY ALTERNATIVE's main result?
Alirocumab reduced mean (standard error) LDL-C by 45.0% (2.2%) vs 14.6% (2.2%) with ezetimibe (mean difference 30.4% [3.1%], P < .0001)
How much did LDL cholesterol change in ODYSSEY ALTERNATIVE?
Baseline mean (SD) LDL-C 191.3 (69.3) mg/dL (5.0 [1.8] mmol/L); alirocumab -45.0% (2.2%) vs ezetimibe -14.6% (2.2%), mean difference 30.4% (3.1%), P<.0001
Related trials
- ODYSSEY FH I and II (2015)In patients with heterozygous familial hypercholesterolemia inadequately controlled on maximally tolerated lipid-lowering therapy, adding alirocumab produced large, durable LDL-C reductions through 78 weeks and was generally well tolerated.
- ODYSSEY LONG TERM (2015)Adding alirocumab to maximally tolerated statin therapy markedly lowered LDL cholesterol and was associated with a post hoc reduction in cardiovascular events, though with somewhat higher rates of injection-site reactions, myalgia, neurocognitive, and ophthalmologic events.
- RUTHERFORD-2 (2015)In patients with heterozygous familial hypercholesterolaemia on stable lipid-lowering therapy, adding evolocumab produced rapid, large LDL cholesterol reductions of about 60% compared with placebo with a tolerability profile similar to placebo.
- TESLA Part B (2015)In patients with homozygous familial hypercholesterolaemia on stable background therapy, adding evolocumab 420 mg every 4 weeks significantly lowered LDL cholesterol compared with placebo and was well tolerated over 12 weeks.
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