Table 2. Major clinical trials of ezetimibe.
| Characteristics | ENHANCE (2008)41 | SEAS (2008)15 | SHARP (2011)11 | IMPROVE-IT (2015)10 |
|---|---|---|---|---|
| Study type | Phase III | Phase III | Phase III | Phase III |
| Drug | Ezetimibe | Ezetimibe | Ezetimibe | Ezetimibe |
| Intervention | Simvastatin 80 mg + ezetimibe vs. simvastatin 80 mg + placebo | Simvastatin 40 mg + ezetimibe vs. simvastatin 40 mg + placebo | Simvastatin 20 mg + ezetimibe vs. simvastatin 20 mg + placebo | Simvastatin 40 mg + ezetimibe vs. simvastatin 40 mg + placebo |
| Study population | 720 patients with familial hypercholesterolemia with untreated LDL cholesterol ≥210 mg/dL | 1,873 patients with mild-to-moderate asymptomatic AS | 9,270 patients with chronic kidney disease without history of MI or coronary revascularization | 18,144 patients who had been hospitalized for an ACS within the preceding 10 days and 50 mg/dL ≤ LDL cholesterol ≤100 mg/dL with lipid lowering therapy or 50 mg/dL ≤ LDL cholesterol ≤125 mg/dL without lipid lowering therapy |
| Median duration of follow-up | 24 mon | 52.2 mon | 4.9 yr | 6 yr |
| Primary efficacy endpoint | Change in the mean carotid-artery intima-media thickness | Composite of MACE: cardiovascular death, AVR, nonfatal MI, hospitalization for unstable angina, HF, CABG, PCI, and non-hemorrhagic stroke | First major atherosclerotic event: non-fatal MI or coronary death, non-hemorrhagic stroke, or any arterial revascularization procedure | Composite of MACE: cardiovascular death, nonfatal MI, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke |
| Results | The mean (±SE) change in the carotid-artery intima-media thickness, was 0.0058±0.0037 mm in the simvastatin-only group and 0.0111±0.0038 mm in the simvastatin-plus-ezetimibe group (p=0.29) | Composite of MACE occurred in 333 patients (35.3%) in the simvastatin-ezetimibe group and in 355 patients (38.2%) in the placebo group (HR, 0.96; p=0.59) | - 17% reduction first major atherosclerotic event in ezetimibe group | 2.0% absolute risk difference: 32.7% in the simvastatin-ezetimibe group, 34.7% in the simvastatin-monotherapy group (HR, 0.936; p=0.016) |
| - 526 (11.3%) in the simvastatin-ezetimibe group and in 619 patients (13.4%) in the placebo group (RR, 0.83; log rank p=0.0021) |
ENHANCE, Efficacy and Safety Study of Prolonged-Release Fampridine in Participants With Multiple Sclerosis; SEAS, Simvastatin and Ezetimibe in Aortic Stenosis; SHARP, Study of Heart and Renal Protection; IMPROVE-IT, IMProved Reduction of Outcomes: Vytorin Efficacy International Trial; LDL, low-density lipoprotein; AS, aortic stenosis; MI, myocardial infarction; ACS, acute coronary syndrome; MACE, major adverse cardiovascular events; AVR, aortic valve replacement; HF, heart failure; CABG, coronary artery bypass graft; PCI, percutaneous coronary intervention; SE, standard error; HR, hazard ratio; RR, relative risk.