Patel 2015.

Study characteristics
Methods	Parallel randomised controlled clinical trial Randomisation ratio: 1:1 Equivalence design: 2‐sided confidence interval Open‐label
Participants	N recruited = 731 N randomised = 623 (312 control, 311 intervention) N reported outcomes = 623 Median age: 63.4 years (intervention), 63.7 years (control) INCLUSION CRITERIA "Men and women aged 18 years at high CVD risk, defined as either established CVD (history of coronary, ischaemic cerebrovascular, or peripheral vascular disease) or an estimated five‐year CVD risk of 15% (using the Framingham risk equation, including a 5% increment for Aboriginal or Torres Strait Islander identification) were eligible. Each participant had to have, in their doctor’s view, indications for all and no contraindications to any component of at least one of two polypills – version 1 (containing aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg, atenolol 50mg) or version 2 (containing aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg)." EXCLUSION CRITERIA "Participants were excluded if it was felt clinically inappropriate to alter medications." COUNTRY/SETTING: Australia STUDY PERIOD: January 2010 ‐ May 2012
Interventions	Number of study centres: 33 Australian centers (12 Aboriginal Medical Services) "Participants attended the primary healthcare centres for trial assessments at randomization and 12 month intervals thereafter. All participants were also reviewed one month post‐randomization and at intervening six month intervals, but these could be conducted by telephone. BP and fasting lipids levels were obtained at baseline, 12 months, 24 months and the final visit (at 36 months)." INTERVENTION GROUP ‐ "polypill‐based strategy received a polypill containing aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg" CONTROL GROUP ‐ ‘usual care’ continued with separate medications and doses as prescribed by their doctor
Outcomes	PRIMARY OUTCOMES: self‐reported combination treatment use, systolic blood pressure and total cholesterol SECONDARY OUTCOMES: "Secondary outcomes included self‐reported combination treatment use at 12 months; combination treatment prescriptions at the study end; reasons for stopping cardiovascular medications; changes in lipid fractions; quality of life; serious adverse events; cardiovascular events (coronary heart disease, heart failure leading to death or hospitalization, cerebrovascular or peripheral arterial disease events); and renal events (new onset microalbuminuria (albumin:creatinine ratio 3.0–33.9mg/mmol), progression to macroalbuminuria (albumin:creatinine ratio >33.9mg/mmol) or at least a 50% decrease in estimated glomerular filtration rate from baseline to a level <60 ml/min per 1.73m2)."
Notes	Commercial funding/non‐commercial funding/other funding: "This work was supported by the National Health and Medical Research Council of Australia (grant numbers 457508, 571281 and 632810). The funder and Dr Reddy’s Laboratories (who provided polypills free of charge for the trial) had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript." Stated aim for study: "Most individuals at high cardiovascular disease (CVD) risk worldwide do not receive any or optimal preventive drugs. We aimed to determine whether fixed dose combinations of generic drugs (‘polypills’) would promote use of such medications."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Central, computer‐based randomization to polypill based strategy or usual care"
Allocation concealment (selection bias)	Low risk	See above
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Unblinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	"The study failed to recruit the numbers of participants originally planned as a result of limited resources and was therefore under‐powered to demonstrate significant differences in BP and cholesterol."
Selective reporting (reporting bias)	Low risk	All outcomes reported