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IMPROVE-IT TRIAL |
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| Problem | Recent acute coronary syndrome with raised LDL |
| Format | Double-blind RCT |
| Treatment | Ezetimibe 10mg + Simvastatin 40mg |
| Control | Placebo + Simvastatin 40mg |
| Population | 18,144 patients |
| Inclusion criteria | - Aleast 50 years of age - Hospitalized within the preceding 10 days for an acute coronary syndrome (an acute myocardial infarction, with or without ST-segment elevation on electrocardiography, or high-risk unstable angina). - LDL cholesterol level of 50 mg per deciliter (1.3 mmol per liter) or higher measured within 24 hours of admission for ACS. |
| Exclusion criteria | For patients on other lipid-lowering therapy, maximum LDL was 100 mg per deciliter (2.6 mmol per liter). For those NOT on other lipid-loweing therapy, maximum LDL cholesterol level for enrollment was 125 mg per deciliter (3.2 mmol per liter). Planned coronary-artery bypass grafting for the acute coronary syndrome event. Creatinine clearance of less than 30 ml per minute. Active liver disease. Use of statin therapy that had LDL cholesterol–lowering potency greater than 40 mg of simvastatin. |
| Follow-up | Median 6 years |
| Primary endpoint | Composite of: - CV death - Major coronary event (nonfatal myocardial infarction, documented unstable angina requiring hospital admission, or coronary revascularization occurring at least 30 days after randomization) - Non-fatal stroke |
| Secondary endpoint(s) | Composite of: -Death from any cause -Major coronary event -Nonfatal stroke Composite of: -Death from coronary heart disease -Nonfatal myocardial infarction -Urgent coronary revascularization 30 days or more after randomization Composite of: -Death from cardiovascular causes -Nonfatal myocardial infarction -Hospitalization for unstable angina -All revascularization 30 days or more after randomization -Nonfatal stroke |
| Details | |
| Brief summary: | Ezetimibe, added to simvastatin in post-ACS patients with high LDL, reduced (ARR 2%) composite of CV death, MI and non-fatal stroke - powered by reduction in MI and ischaemic stroke. |
| PAPER: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. | |
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| Date | 18 Jun 2015 |
| Journal | N Engl J Med. 2015 Jun 18;372(25):2387-97. doi: 10.1056/NEJMoa1410489. |
| Information | When added to simvastatin 40mg (arguably an out-dated statin) in patients with recent ACS and a raised LDL, ezetimibe reduced the composite of cardiovascular death, non-fatal MI and non-fatal stroke. This was largely powered by a reduction in MI (p < 0.01) and ischaemic stroke (p < 0.01). Some have argued the benefits are modest (ARR 2.0%) in a background rate of around a third of patients at 3 years - see http://www.medscape.com/viewarticle/846502 An editorial has argued there is nothing special about ezetimibe, and instead that the study supports the LDL hypothesis, that all LDL-lowering therapies are equal in outcomes, and that simvastatin + ezetimibe as reasonable an option as a high-potency statin - see http://www.nejm.org/doi/full/10.1056/NEJMe1507041 |