GLAGOV.

Study characteristics
Methods	Type of RCT: 1:1 parallel‐group, double‐blind RCT Settings: outpatient care Duration: 76 weeks Start and stop dates: April 2013 and July 2016
Participants	Number of participants: 968 Number lost to follow‐up: 124 participants excluded from the primary analysis Women:  269 (28%) Mean age (SD), years: 59.8 (9.2) History of CVD: 628 (65%) Participants with FH: unknown Inclusion criteria Men or women aged > 18 years Clinically indicated coronary angiogram, evidence of coronary disease Stable statin dose for ≥ 4 weeks prior to screening LDL‐C criteria met within 4 weeks of screening visit or, if applicable, at the end of lipid stabilisation period: LDL‐C ≥ 80 mg/dL, OR LDL‐C ≥ 60 but ≤ 80 mg/dL in the presence of 1 major or 3 minor risk factors Major risk factors (1 required): non‐coronary atherosclerotic vascular disease as evidenced by documented peripheral arterial disease, documented abdominal aortic aneurysm, or documented cerebrovascular disease; documented myocardial infarction or hospitalisation for unstable angina within the last 2 years; documented T2DM Minor risk factors (3 required): cigarette smoking (current); hypertension (blood pressure ≥ 140/90 mmHg or current use of antihypertensive medications); low HDL‐C (men: < 40 mg/dL; women < 50 mg/dL); family history of premature CHD (first‐degree male relative aged < 55 years or first‐degree female relative aged < 65 years); age (men ≥ 50 years; women ≥ 55 years); hs‐CRP ≥ 2 mg Exclusion criteria Clinically significant heart disease which, in the opinion of the principal investigator, is likely to require coronary bypass surgery, percutaneous coronary intervention, cardiac transplantation, surgical valve repair, replacement during the study, or a combination of these Heart failure of New York Heart Failure Association (NYHA) class III or IV or last known left ventricular ejection fraction < 30% Coronary artery bypass surgery < 6 week prior to the qualifying IVUS Cardiac arrhythmia within 3 months prior to randomisation that was not controlled by medication Uncontrolled hypertension at day 1, defined as a resting systolic blood pressure ≥ 180 mmHg TG > 400 mg/dL at screening Type 1 diabetes mellitus or poorly controlled T2DM (HbA1c 9%) at screening TSH lower limit of normal or TSH > 1.5 × ULN Estimated glomerular filtration rate < 30 mL/minute per 1.73 m² Aspartate aminotransferase or alanine aminotransferase > 2 × ULN Creatine kinase > 3 × ULN Use of cholesterylester transfer protein inhibition treatment within 12 months prior to randomisation Any prior use of PCSK9 inhibitor therapy Consumption of any of the following drugs for more than 2 weeks in the last 3 months prior to LDL‐C screening: systemic ciclosporin, systemic steroids, isotretinoin History of malignancy (except non‐melanoma skin cancers, cervical in situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) Known major active infection, or major haematological, renal, metabolic, gastrointestinal, or endocrine dysfunction Baseline IVUS did not meet IVUS core laboratory technical standards Women could not be pregnant or breastfeeding. Premenopausal women must have been willing to use ≥ 1 highly effective method of birth control during treatment and for an additional 15 weeks after end of treatment
Interventions	Background therapy: statin Randomised therapy: evolocumab vs placebo. Evolocumab dose: 140 mg/2 week or to 420 mg/4 weeks. Resulting in a 2‐week equivalent dose of 140–210 mg
Outcomes
Notes	Funded by Amgen
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study did not describe this in detail. However, Amgen trials used interactive voice‐response system which was likely used here as well.
Allocation concealment (selection bias)	Unclear risk	Not reported. However, Amgen trials used interactive voice‐response system which was likely used here as well.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Described as double‐blind. Quote: "Technicians blinded to the treatment status of the patient and the timing of each individual pullback will perform the analysis."
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "The study includes adjudication of deaths and specific cardiovascular events potential endpoints (PEPs) by an independent Clinical Events Committee (CEC) and formal review of the accumulating data by an independent Data Monitoring Committee (DMC)."
Incomplete outcome data (attrition bias) All outcomes	High risk	124/970 participants excluded from the primary analysis.
Selective reporting (reporting bias)	Low risk	Reported the usual endpoints.
Other bias	Low risk	No concerns outside the assessed risk of bias domains.