article139

ODYSSEY LONG TERM

"Alirocumab for Hypercholesterolemia in Statin-Treated Patients". The New England Journal of Medicine. Published March 15, 2015.

Clinical Question

Does alirocumab improve LDL cholesterol levels in patients at high risk for cardiovascular events who are already receiving their maximum tolerated dose of statins?

Bottom Line

In patients at high risk for cardiovascular events, treatment with alirocumab significantly reduced LDL cholesterol levels when added to statin therapy at the maximum tolerated dose. A post hoc analysis suggested a reduction in the rate of cardiovascular events with alirocumab.

Major Points

Guidelines

Updated guidelines will need to reflect the results of this trial and other ongoing studies to provide recommendations on the use of PCSK9 inhibitors in the management of hypercholesterolemia in statin-treated patients.

Design

- Multicenter, double-blind, placebo-controlled, parallel-group, randomized clinical trial
- N=2341 patients at high risk for cardiovascular events
- Randomized in a 2:1 ratio to alirocumab (150 mg every 2 weeks) or placebo
- Trial duration: 78 weeks
- Enrollment: N/A
- Analysis: Intention-to-treat
- Primary efficacy outcome: Percentage change in calculated LDL cholesterol level from baseline to week 24

Population

- Inclusion Criteria: High-risk patients with calculated LDL cholesterol levels ≥70 mg per deciliter (1.8 mmol per liter), receiving maximum tolerated dose of statins, with or without other lipid-lowering therapy
- Exclusion Criteria: N/A
- Baseline Characteristics: Mean age 60 years, 37.8% women, 68.9% had a history of coronary heart disease, 17.7% had heterozygous familial hypercholesterolemia

Interventions

- Alirocumab 150 mg or placebo administered as a subcutaneous injection every 2 weeks

Outcomes

- Primary: At week 24, alirocumab group had a 62 percentage point reduction in LDL cholesterol from baseline, compared to 0.8% in the placebo group (P<0.001)
- Secondary: Consistent LDL reduction observed over 78 weeks
- Safety: Higher rates of injection-site reactions, myalgia, neurocognitive events, and ophthalmologic events with alirocumab
- Cardiac events: Post hoc analysis showed a lower rate of major adverse cardiovascular events in the alirocumab group

Criticisms

- Short relative duration for a chronic treatment
- Post hoc nature of cardiovascular outcomes analysis
- Lack of long-term safety and efficacy data

Funding

- Funded by Sanofi and Regeneron Pharmaceuticals