ODYSSEY OPTIONS II

Methods	Type of RCT: double‐blind, placebo‐controlled, parallel‐group RCT Settings: outpatient care Duration: 24 weeks Start and stop dates: NA
Participants	Number of participants: 305 Number lost to follow‐up: 7 Women: 118 (39%) Age (SD), years: 61 (10) History of CVD: 177 (58%) Participants with FH: 41 (13%) Participants with a history of CVD and LDL‐C levels ≥ 70 mg/dL, or CVD risk factors and LDL‐C ≥ 100 mg/dL
Interventions	Background therapy: Patients received 24 weeks 10 or 20 mg of baseline rosuvastatin and National Cholesterol Education Program Adult Treatment Panel III Randomised therapy: alirocumab vs add‐on 10 mg ezetimibe per day, or additional 10 or 20 mg of rosuvastatin Alirocumab dose: add‐on of 75 mg alirocumab every 2 weeks, with uptitration of alirocumab to 150 mg at week 12. Resulting in a 2‐week equivalent dose of 75 mg to 150 mg Resulting in 6 groups 10 mg rosuvastatin plus 75 mg alirocumab every 2 weeks 10 mg rosuvastatin plus 10 mg ezetimibe every day 10 mg rosuvastatin plus 10 mg rosuvastatin every day 20 mg rosuvastatin plus 75 mg alirocumab every 2 weeks 20 mg rosuvastatin plus 10 mg ezetimibe every day 20 mg rosuvastatin plus 20 mg rosuvastatin every day All blinded with placebo alirocumab and over‐encapsulated tables for ezetimibe, rosuvastatin
Outcomes	CVD, lipids, any adverse events, all‐cause mortality
Notes	Unless otherwise specified, comparisons are made of alirocumab therapy vs pooled other therapies Fasting blood samples were collected in the morning LDL‐C was calculated using the Friedewald formula Lipoprotein(a) was analysed using an immunoradiometric assay on the Siemens BNII NCT01730053
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Centralised interactive voice‐response system or interactive Web‐response system
Allocation concealment (selection bias)	Low risk	Permuted‐block design and central allocation
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	2 (1.94%) participants in the alirocumab arm had missing lipid measurements compared with 5 (2.48%) in the comparator arms. 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