ODYSSEY FH I.

Study characteristics
Methods	Type of RCT: 2:1 parallel‐group, double‐blind, stratified RCT Settings: outpatient care Duration: 78 weeks Start and stop dates: July 2012 and December 2014
Participants	Number of participants: 486 Number lost to follow‐up: 1 Women: 212 (44%) Mean age (SD), years: 52 (13) History of CVD: 225 (46%) Participants with FH: 485 (100%) Participants with heFH on a maximally tolerated dose of statin with LDL‐C ≥ 70 mg/dL or ≥ 100 mg/dL, depending on CV risk
Interventions	Background therapy: add‐on to maximal tolerated dose of statin and possible addition of other LLTs Randomised therapy: alirocumab vs placebo Alirocumab dose: 78 weeks of 75 mg every 2 weeks, with possible uptitration to 150 mg every 2 weeks at week 12. Resulting in a 2‐week equivalent dose of 75–150 mg
Outcomes	CVD, adverse events, all‐cause mortality
Notes	LDL‐C calculated using Friedewald formula, or if TGs > 400 mg/dL via beta quantification method NCT01623155 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	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	1 (0.31%) participant in the alirocumab arm had missing lipid measurements compared with 0 in the comparator arm. 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.