IMPROVE-IT
Trial question
What is the effect of the addition of ezetimibe to statin therapy in patients who have been hospitalized for an acute coronary syndrome?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
24.0% female
76.0% male
N = 18144
18144 patients (4416 female, 13728 male).
Inclusion criteria: patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg/dL.
Key exclusion criteria: planned CABG for the acute coronary syndrome event, CrCl of < 30 mL/min, active liver disease, or use of statin therapy that had LDL cholesterol-lowering potency > 40 mg of simvastatin.
Interventions
N=9067 simvastatin-ezetimibe (simvastatin at a dose of 40 mg plus ezetimibe at a dose of 10 mg, once daily).
N=9077 simvastatin monotherapy once daily (simvastatin at a dose of 40 mg plus placebo).
Primary outcome
CV death, major coronary event, or nonfatal stroke, Kaplan-Meier event rate at 7 years
32.7%
34.7%
34.7 %
26.0 %
17.4 %
8.7 %
0.0 %
Simvastatin-ezetimibe
Simvastatin monotherapy once
daily
Significant
decrease ▼
NNT = 50
Significant decrease in CV death, major coronary event, or nonfatal stroke, Kaplan-Meier event rate at 7 years (32.7% vs. 34.7%; HR 0.936, 95% CI 0.89 to 0.99).
Secondary outcomes
Significant increase in median time-weighted average LDL cholesterol level (53.2 vs. 69.9; difference 16.7, 95% CI -17.49 to -16.02).
Safety outcomes
No significant differences in rates of prespecified muscle, gallbladder, and hepatic adverse events and cancer.
Conclusion
In patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg/dL, simvastatin-ezetimibe was superior to simvastatin monotherapy once daily with respect to CV death, major coronary event, or nonfatal stroke, Kaplan-Meier event rate at 7 years.
Reference
Cannon CP, Blazing MA, Giugliano RP et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015 Jun 18;372(25):2387-97.
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