SHARP trial

526 [11·3%] simvastatin plus ezetimibe vs 619 [13·4%] placebo; rate ratio [RR] 0·83, 95% CI 0·74-0·94; log-rank p=0·0021

average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance)

Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4·6%] vs 230 [5·0%]; RR 0·92, 95% CI 0·76-1·11; p=0·37); significant reductions in non-haemorrhagic stroke (131 [2·8%] vs 174 [3·8%]; RR 0·75, 95% CI 0·60-0·94; p=0·01) and arterial revascularisation procedures (284 [6·1%] vs 352 [7·6%]; RR 0·79, 95% CI 0·68-0·93; p=0·0036); no significant excess of death from any non-vascular cause (668 [14·4%] vs 612 [13·2%], p=0·13)

Excess risk of myopathy was only two per 10,000 patients per year of treatment with this combination (9 [0·2%] vs 5 [0·1%]); no evidence of excess risks of hepatitis (21 [0·5%] vs 18 [0·4%]), gallstones (106 [2·3%] vs 106 [2·3%]), or cancer (438 [9·4%] vs 439 [9·5%], p=0·89)

“Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance) during a median follow-up of 4·9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11·3%] simvastatin plus ezetimibe vs 619 [13·4%] placebo; rate ratio [RR] 0·83, 95% CI 0·74-0·94; log-rank p=0·0021).”

Quoted from the abstract of Lancet 2011, checked word for word against PubMed. PubMed 21663949 · Full paper (DOI)

• 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.
• IMPROVE-IT (2015)Adding ezetimibe to statin therapy after acute coronary syndrome modestly reduces cardiovascular events beyond statin alone, with similar safety.
• 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.
• 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.