ODYSSEY OPTIONS II.

Study characteristics
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%) Mean age (SD), years: 61 (10) History of CVD: 177 (58%) Participants with FH: 41 (13%) Participants with history of CVD and LDL‐C levels ≥ 70 mg/dL, or CVD risk factors and LDL‐C ≥ 100 mg/dL
Interventions	Background therapy: participants received 24 weeks baseline rosuvastatin 10 mg or 20 mg and National Cholesterol Education Program Adult Treatment Panel III Randomised therapy: alirocumab vs add‐on ezetimibe 10 mg/day, or additional rosuvastatin 10 mg or 20 mg Alirocumab dose: add‐on of 75 mg every 2 weeks, with uptitration to 150 mg at week 12. Resulting in a 2‐week equivalent dose of 75–150 mg Resulting in 6 groups rosuvastatin 10 mg plus alirocumab 75 mg every 2 weeks rosuvastatin 10 mg plus ezetimibe 10 mg every day rosuvastatin 10 mg plus rosuvastatin 10 mg every day rosuvastatin 20 mg plus alirocumab 75 mg every 2 weeks rosuvastatin 20 mg plus ezetimibe every day rosuvastatin 20 mg plus rosuvastatin 20 mg every day All blinded with placebo alirocumab and overencapsulated tables for ezetimibe, rosuvastatin
Outcomes	CVD, any adverse events, all‐cause mortality
Notes	Unless otherwise specified, comparisons were made of alirocumab therapy vs pooled other therapies Fasting blood samples were collected in the morning LDL‐C calculated using Friedewald formula Lipoprotein(a) was analysed using an immunoradiometric assay on the Siemens BNII NCT01730053 Funded by Sanofi and Regeneron
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) All outcomes	Low risk	Both blinded.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Endpoint adjudication was blinded and 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	Reported protocol‐defined endpoints.
Other bias	Low risk	No concerns outside the assessed risk of bias domains.