FOURIER

Methods	Type of RCT: 1:1 parallel‐group, double‐blind RCT Settings: outpatient care Duration: 157 weeks (36 months) Start and stop dates: 02/2013; 11/2016
Participants	Number of participants: 27,564 (39 did not receive treatment) Number lost to follow‐up: 1558 participants had observed LDL‐C measurements at 36 months, 1375 completed follow‐up time of 36 months for the primary endpoint of CVD Women: 6769 (25%) Age (SD), years: 63 (9) History of CVD: 27,564 (100%), not reported but inferred on the basis of inclusion criteria Participants with FH: NA Inclusion criteria Male or female ≥ 40 to ≤ 85 years of age History of clinically evident cardiovascular disease at high risk for a recurrent event Fasting LDL‐C ≥ 70 mg/dL (≥ 1.8 mmol/L) ) or non‐HDL‐C ≥ 100 mg/dL (> 2.6 mmol/L) Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L) Exclusion criteria NYHA class III or IV, or last known left ventricular ejection fraction < 30% Uncontrolled hypertension Uncontrolled or recurrent ventricular tachycardia Untreated hyperthyroidism or hypothyroidism Homozygous familial hypercholesterolaemia LDL or plasma apheresis
Interventions	Background therapy: statin therapy. Randomized therapy: evolocumab compared to placebo. RUG7652 dose: 140 mg/2w or to 420 mg/4w of evolocumab. Resulting in a two week equivalent dose of 140mg‐210mg.
Outcomes	LDL‐C, any adverse events, CVD, all‐cause mortality, T2DM
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Central computerized system
Allocation concealment (selection bias)	Low risk	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 and blinded adjudication
Incomplete outcome data (attrition bias) All outcomes	Low risk	27564 patients were randomized of whom 39 did not receive any treatment. The number of participants available reduced considerably over time to only 1375 subjects remaining at study end. However, as reported loss to follow‐up was only 0.1% and the decrease in number reflects different enrolment times.
Selective reporting (reporting bias)	Low risk	Reports on most endpoints
Other bias	High risk	Amgen