"Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes". The New England Journal of Medicine. 2015. 372:2387-2397. PubMed • Full text • PDF
Clinical Question
Does the addition of ezetimibe to statin therapy in patients with a recent acute coronary syndrome reduce the rate of cardiovascular events?
Bottom Line
In patients with recent acute coronary syndrome and LDL cholesterol levels within guideline recommendations, the addition of ezetimibe to statin therapy resulted in incremental lowering of LDL cholesterol and a further reduction in the risk of cardiovascular events without significant safety concerns.
Major Points
Guidelines
At the time of patient enrollment, guidelines recommended LDL cholesterol levels of less than 70 mg per deciliter for patients post-acute coronary syndrome. These current findings suggest additional benefits with even lower LDL cholesterol levels.
Design
Double-blind, randomized control trial with median follow-up of 6 years.
Population
18,144 patients, ≥50 years old, hospitalized within preceeding 10 days for acute coronary syndrome and with LDL cholesterol levels of 50-125 mg per deciliter (or 50-100 mg per deciliter if already on lipid-lowering therapy).
Interventions
- Simvastatin (40 mg) + Ezetimibe (10 mg) [simvastatin–ezetimibe group]
- Simvastatin (40 mg) + Placebo [simvastatin-monotherapy group]
Outcomes
Primary Outcome:
- Composite of cardiovascular death, major coronary event, or nonfatal stroke
Secondary Outcomes:
- Composite of death from any cause, major coronary event, or nonfatal stroke
- Composite of death from coronary heart disease, nonfatal myocardial infarction, or urgent coronary revascularization ≥30 days after randomization
- Composite of death from cardiovascular causes, nonfatal myocardial infarction, hospitalization for unstable angina, all revascularization ≥30 days after randomization, or nonfatal stroke
Criticisms
- Study only included patients with acute coronary syndrome; results are most applicable to this population.
- Study statin regimen may not represent contemporary high-intensity statin therapy, as only simvastatin 40 mg and 80 mg were used.
Funding
Merck (the sponsor and manufacturer of ezetimibe).
Further Reading
- Cholesterol Treatment Trialists (CTT) Collaborators. Am J Cardiol. 2014.
- Sabatine MS, et al. N Engl J Med. 2015.