Cardiovascular outcome trial · N Engl J Med 2015
IMPROVE-IT trial
Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes.
The bottom line
Adding ezetimibe to statin therapy after acute coronary syndrome modestly reduces cardiovascular events beyond statin alone, with similar safety.
BenefitUS status: US-approved
At a glance
- Medicine
- Simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe)
- Compared with
- Simvastatin (40 mg) and placebo (simvastatin monotherapy)
- People
- 18,144
- Who took part
- Patients hospitalized for an acute coronary syndrome within the preceding 10 days with LDL cholesterol levels of 50 to 100 mg per deciliter (if receiving lipid-lowering therapy) or 50 to 125 mg per deciliter (if not receiving lipid-lowering therapy)
- Design
- double-blind, randomized trial
- Follow-up
- median follow-up was 6 years
- Main question
- A composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke
Main result
Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P=0.016)
Effect on LDL cholesterol
The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001).
Safety
Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups.
In the trial's own words
“The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P=0.016).”
Quoted from the abstract of N Engl J Med 2015, checked word for word against PubMed. PubMed 26039521 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Ezetimibe (Zetia)
Common questions
What did the IMPROVE-IT trial find?
Adding ezetimibe to statin therapy after acute coronary syndrome modestly reduces cardiovascular events beyond statin alone, with similar safety.
Who was in IMPROVE-IT?
18,144 people. Patients hospitalized for an acute coronary syndrome within the preceding 10 days with LDL cholesterol levels of 50 to 100 mg per deciliter (if receiving lipid-lowering therapy) or 50 to 125 mg per deciliter (if not receiving lipid-lowering therapy).
What was IMPROVE-IT's main result?
Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P=0.016)
How much did LDL cholesterol change in IMPROVE-IT?
The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001).
Related trials
- SHARP (2011)In patients with moderate-to-severe chronic kidney disease, lowering LDL cholesterol with simvastatin plus ezetimibe safely reduced major atherosclerotic events compared with placebo.
- EWTOPIA 75 (2019)In patients aged 75 or older with elevated LDL-C and no history of coronary disease, adding ezetimibe to usual care reduced cardiovascular events, though open-label design, early termination, and follow-up issues warrant cautious interpretation of the benefit's magnitude.
- SEAS (2008)In patients with mild-to-moderate asymptomatic aortic stenosis, simvastatin plus ezetimibe did not reduce the composite of aortic-valve and ischemic cardiovascular events, though it reduced ischemic events alone and was associated with more cancer cases.
- RACING (2022)In patients with atherosclerotic cardiovascular disease, moderate-intensity rosuvastatin plus ezetimibe was non-inferior to high-intensity rosuvastatin alone for 3-year cardiovascular outcomes, achieved more patients with LDL under 70 mg/dL, and caused less drug intolerance-related discontinuation or dose reduction.
Get your LDL treated to a goal
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