PILL 2011.

Methods	Individual‐level RCT
Participants	378 participants (189 intervention; 189 comparator) from 7 countries (Australia, Brazil, India, Netherlands, New Zealand, UK, USA) with 5‐year Framingham coronary heart disease risk ≥ 7.5% or if Framingham risk was between 5% and 7.5%, two or more additional untreated risk factors were needed (body mass index > 30 kg/m2, waist circumference > 102 cm in men or > 88 cm in women; heart rate > 80 bpm; fasting glucose 5.6 mmol/L‐7 mmol/L, triglycerides > 1.7 mmol/L; family history of first degree relative with premature ischaemic heart disease or stroke (men < 55 years; women: < 65 years), or glomerular filtration rate < 60mL/min
Interventions	Intervention: Red heart pill (aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) Comparator: placebo
Outcomes	Change in SBP; change in LDL‐C; tolerability; secondary outcomes included discontinuation, DBP, total cholesterol, HDL‐C, total cholesterol:HDL cholesterol ratio, non‐HDL cholesterol, triglycerides, frequency of switching/adding open‐label treatment, estimated effects on CVD risk
Notes	Comparator: inactive/placebo
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Central computer‐based randomisation
Allocation concealment (selection bias)	Low risk	Central computer‐based randomisation
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Specifically reported and use of placebo control
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessors and study staff all blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Low rates of loss to follow‐up (experimental 2%; control 1%); however, last observation carried forward method used for missing continuous data at week 12
Selective reporting (reporting bias)	Low risk	Outcomes outlined in methods paper were reported in the primary manuscript
Other bias	Low risk	No other sources of bias are identifiable