TIPS 2009.

Methods	Individual‐level RCT
Participants	2053 participants (205 aspirin; 205 thiazide; 209 thiazide + ramipril; 207 thiazide + atenolol; 205 ramipril + atenolol; 204 thiazde + ramipril + atenolol; 204 thiazide + ramipril + atenolol + aspirin; 202 simvastatin; 412 Polycap [thiazide + ramipril + atenolol + simvastatin + aspirin); 45‐80 years old without prior cardiovascular disease but with at least one risk factor: type 2 diabetes; blood pressure > 140/90 mmHg but < 160/100 mmHg; smoker within the past five years; waist‐to‐hip ratio > 0.85 for women and 0.90 for men; LDL cholesterol > 3.1 mmol/L but less 4.5 mmol/L or HDL cholesterol < 1.04 mmol/L
Interventions	Intervention: Polycap (thiazide 12.5 mg, atenolol 50 mg, ramipril 5 mg, simvastatin 20 mg, aspirin 100 mg) Comparator: 8 other drug/drug combination groups listed above
Outcomes	LDL for the effect of lipid‐lowering drugs, BP for antihypertensive drugs, heart rate for the effects of atenolol, urinary 11‐dehydrothromboxane B2 for the antiplatelet effects of aspirin, rates of discontinuation of drugs for safety
Notes	Comparator: active
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Central computer randomisation
Allocation concealment (selection bias)	Low risk	Central computer randomisation
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Placebo control using identical capsule
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double‐blinding reported; probably occurred given research team's prior studies
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Unclear how missing SBP and LDL‐C data at week 12 follow‐up were handled
Selective reporting (reporting bias)	Low risk	Primary outcomes reported
Other bias	Low risk	No other sources of bias are identifiable