ODYSSEY OUTCOMES.

Study characteristics
Methods	Type of RCT: 1:1 double‐blind, stratified, placebo‐controlled, parallel‐group RCT (with run‐in phase) Settings: outpatient care Duration: median follow‐up 2.8 years Start and stop dates: August 2012 and January 2018
Participants	Number of participants: 18,924 Number lost to follow‐up: 86 Women: 4762 (25%) Mean age (SD), years: 59 (9) History of CVD: 0 Participants with FH: NA People aged ≥ 40 years had been hospitalised with an acute coronary syndrome (myocardial infarction or unstable angina) 1–12 months before randomisation, and had LDL‐C ≥ 70 mg/dL (1.8 mmol/L), non‐HDL‐C ≥ 100 mg/dL, or ApoB level ≥ 80 mg/dL
Interventions	Background therapy: minimum of 2 weeks of stable treatment with atorvastatin 40–80 mg once daily, rosuvastatin 20–40 mg once daily, or maximum tolerated dose of 1 of these statins (including no statin in the case of documented unacceptable adverse effects) Randomised therapy: alirocumab vs placebo Alirocumab dose: 75 mg every 2 weeks followed by blinded, lipid‐guided adjustment.
Outcomes	CVD, defined as a composite of: death from CHD, non‐fatal myocardial infarction, unstable angina requiring hospitalisation, and ischaemia‐driven coronary revascularisation
Notes	Funded by Sanofi and Regeneron
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Centralised treatment allocation system. Quote: "the Interactive Voice Response System (IVRS) and the Interactive Web Response System (IWRS) depending on the choice of the site."
Allocation concealment (selection bias)	Low risk	Placebo controlled.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "The trial‐group assignments and lipid levels during the trial were concealed from the patients and investigators."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Independent Clinical Events Committee
Incomplete outcome data (attrition bias) All outcomes	Low risk	86/18,924 participants lost to follow‐up.
Selective reporting (reporting bias)	Low risk	Reported protocol‐defined endpoints.
Other bias	Low risk	No concerns outside the assessed risk of bias domains.