ODYSSEY Long Term.

Study characteristics
Methods	Type of RCT: 2:1 parallel‐group, double‐blind RCT with stratified randomisation Settings: outpatient care Duration: 78 weeks Start and stop dates: January 2012 and November 2014
Participants	Number of participants: 2341 Number lost to follow‐up: 247 Women: 884 (38%) Mean age (SD), years: 63 (11) History of CVD: 1607 (68%) Participants with FH: 415 (18%) Participants with heFH or established CHD or CHD risk equivalent
Interventions	Background therapy: SOC Randomised therapy: alirocumab vs placebo for 78 weeks Alirocumab dose: 150 mg every 2 weeks
Outcomes	CVD, adverse events, all‐cause mortality
Notes	Blood samples were obtained after a 10‐hour overnight fast Total cholesterol, TGs, and HDL‐C levels in serum were determined via CDC, National Heart Lung Blood Institute Lipid Standardization Program assays LDL‐C calculated using Friedewald formula at all sampling points. LDL‐C was also measured via ultracentrifugation and precipitation (beta‐quantification) by the central laboratory at weeks 0, 12, 24, 52, and 78, and in cases where TG values were > 400 mg/dL ApoB, apolipoprotein A1, and lipoprotein(a) levels in serum were determined via immunonephelometry NCT01507831 Funded by Sanofi and Regeneron
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Central computer‐generated allocation system.
Allocation concealment (selection bias)	Low risk	Central computer‐generated allocation system.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants and investigators were blinded with placebo identically packaged as alirocumab.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Biomarkers assessed at a central laboratory blinded for allocation. Clinical endpoints and adverse advents were similarly assessed in a blinded method.
Incomplete outcome data (attrition bias) All outcomes	High risk	ITT analysis excluded participants (167 (10.8%) in the intervention arm and 80 (10.1%) in the control arm) who missed LDL‐C measurements during first 24 weeks. In total, 437 alirocumab participants did not complete study follow‐up compared with 193 placebo participants. Categorical outcomes were analysed using an available‐case analysis. Missing biomarker values were imputed using mixed models or multiple imputations.
Selective reporting (reporting bias)	Low risk	Reported protocol‐defined endpoints.
Other bias	Low risk	No concerns outside the assessed risk of bias domains.