Rossebø 2008.

Methods	Randomised, double‐blind, placebo‐controlled trial.
Participants	Men and women between the ages of 45 and 85 years (mean of age = 67.9) who had asymptomatic, mild to moderate aortic valve stenosis, as assessed on echocardiography, with peak aortic jet velocity of 2.5 to 4 m/s. 1873 participants were randomised. The minimum follow‐up was 4 years (median = 52.2 months). Baseline Characteristics of Participants: Men = 61.5% (simvastatin plus ezetimibe group) and 61.2 % (placebo group). Bicuspid Aortic Valve = 5% (simvastatin plus ezetimibe group) and 6.3% (placebo group). Peak Pressure Gradient, mean (± SD) mmHg = 39.3 (± 13.9) (simvastatin plus ezetimibe group) and 39.6 (± 8.7) (simvastatin plus ezetimibe group). Mean Pressure Gradient, mean (± SD) mmHg = 22.7 (± 8.8) (simvastatin plus ezetimibe group) and 23 (± 13.8) (simvastatin plus ezetimibe group). Aortic Valve Area, mean (± SD) cm² = 1.29 (± 0.48) (simvastatin plus ezetimibe group) and 1.27 (± 0.46) (placebo group). Peak Aortic Jet Velocity, mean (± SD) m/s = 3.09 (± 0.55) (simvastatin plus ezetimibe arm) and 3.10 (± 0.54) (placebo arm). Most of the participants were white and had hypertension. Former smoking = 37% (simvastatin plus ezetimibe group) and 35 %(placebo group). Neoplasm = 11% (simvastatin plus ezetimibe group ) and 8.4% (placebo group). β‐blocker and Aspirin use: 28% (simvastatin plus ezetimibe group) and 25% (placebo group). Calcium antagonist use = 17% (simvastatin plus ezetimibe group) and 16% (placebo group). Diuretic (including spironolactone) = 22% (simvastatin plus ezetimibe group) and 28% (placebo group). The mean of left ventricular ejection fraction was 66% for both groups. LDL value, (± SD) = 139 mg/dL (± 35) (simvastatin plus ezetimibe group) and 140 mg/dL (±36) (placebo group).
Interventions	Simvastatin (40 mg) plus ezetimibe (10 mg) (n = 944) or matching placebo (n = 929).
Outcomes	Primary outcome: death from cardiovascular causes, aortic valve replacement, congestive heart failure, non‐fatal myocardial infarction, hospitalisation for unstable angina, coronary artery bypass grafting, percutaneous coronary intervention, or non‐haemorrhagic stroke. Secondary outcome: All primary outcomes above and progression of aortic stenosis as seen on echocardiography and safety of the study drugs.
Notes	173 study sites in seven European countries. The authors received support from Merck.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Does not mention how the random sequence generation was carried out.
Allocation concealment (selection bias)	Unclear risk	Does not mention how the allocation concealment was carried out.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants and investigators were blinded.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The Committee members who evaluated all outcomes were blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	The number of withdrawals were reported.
Selective reporting (reporting bias)	Low risk	Study protocol is available and well‐described.
Other bias	High risk	The study was provided by Merck, but the scientific responsibility remained with the independent steering committee.