|
Table 1: Summary the main clinical studies that evaluated combined therapy with ezetimibe and statin vs statin alone. |
|||
|
Study |
ENHANCE (2008) Phase III |
SHARP (2011) Phase III |
IMPROVE-IT (2015) Phase III |
|
Intervention |
Simvastatin 80 mg daily or a combination of simvastatin 80 mg + ezetimibe 10 mg daily |
Simvastatin 20 mg vs ezetimibe/simvastatin 10 mg/20 mg |
Simvastatin 40 mg vs ezetimibe/simvastatin 10 mg/40 mg |
|
Patient population |
720 patients with familial hypercholesterolemia and LDL-C ≥ 210 mg/dL |
9,270 patients with chronic kidney disease with no known history of myocardial infarction or coronary revascularisation |
18,144 patients hospitalized in the last 10 days for an ACS, who were 50 years or older, low-density lipoprotein levels between 50 and 100 mg/dL if they received lipid-lowering therapy or 50 to 125 mg/dL if they did not receive lipid-lowering therapy |
|
Duration |
24 months |
4.9 years |
6 years |
|
Primary endpoint |
Increase in carotid intima-media thickness (cIMT) |
Major vascular events (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure) and progression to ESRD (in nondialysis patients) |
Composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥ 30 days after randomization), or nonfatal stroke |
|
Results |
Change in the cIMT was 0.0058 ± 0.0037 mm in the simvastatin-only group and 0.0111 ± 0.0038 mm in the combined-therapy group |
Combined therapy produced a 17% proportional reduction in major atherosclerotic events (11.3% simvastatin plus ezetimibe vs 13·4% placebo; rate ratio [RR] 0·83, 95% CI 0·74-0·94; log-rank p = 0.0021) |
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) |