ODYSSEY COMBO II

Methods	Type of RCT: 2:1 parallel‐group, double‐blind, stratified, permuted‐block RCT Settings: outpatient care Duration: 104 weeks Start and stop dates: 08/2012 and 07/2015
Participants	Number of participants: 720 Number lost to follow‐up: 13 Women: 190 (26%) Age (SD), years: 62 (9) History of CVD: 649 (90%) FH participants: 0 Participants with hypercholesterolaemia (not defined) and established CHD or CHD risk equivalents (Ischaemic stroke, peripheral artery disease, moderate chronic kidney disease, or diabetes mellitus plus 2 or more additional risk factors) and on a maximally tolerated dose of statin, without addition of other lipid‐lowering therapies
Interventions	Background therapy: add‐on to maximal tolerated dose of statin Randomised therapy: alirocumab and ezetimibe placebo vs 10 mg daily of ezetimibe and placebo Alirocumab: 104 weeks of 75 mg alirocumab every 2 weeks, with uptitration of alirocumab to 150 mg every 2 weeks at week 12, resulting in a 2‐week equivalent dose of 75 mg to 150 mg
Outcomes	CVD, lipids, any adverse events, all‐cause mortality
Notes	LDL‐C was calculated using the Friedewald formula, or if triglycerides exceeded 400 mg/dL, via the beta quantification method NCT01644188 Still ongoing, results are for 52 weeks
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Using an interactive voice‐response system
Allocation concealment (selection bias)	Low risk	Permuted blocks
Blinding of participants and personnel (performance bias) LDL‐C	Low risk	Both were blinded
Blinding of outcome assessment (detection bias) LDL‐C	Low risk	Central laboratory
Incomplete outcome data (attrition bias) All outcomes	Low risk	12 (2.51%) participants in the alirocumab arm had missing lipid measurements compared with 1 (0.41) in the comparator arm. Additionally, mixed‐effects (ANCOVA) models were used
Selective reporting (reporting bias)	Low risk	Reports on protocol‐defined endpoints
Other bias	High risk	Funded by Sanofi and Regeneron