FOCUS 2014.

Methods	"randomized, open‐label, active‐controlled, piggyback, 2‐group parallel trial"
Participants	695 participants (350 polypill; 345 comparator) across 63 sites in 4 countries (Argentina, Italy, Paraguay, Spain) Details about Phase 2 participants (age, sex) not provided in the primary manuscript. Inclusion criteria: “The study population included men and women age > 40 years with a history of acute MI within the last 2 years...Due to slow recruitment, after the initial 591 participants had been included, an amendment to the initial protocol was approved to allow for the inclusion of patients with any past history of an acute MI, regardless of duration from enrollment.” Exclusion criteria: "secondary dyslipidemia, contraindication to any of the components of the polypill, participation in another trial, previous percutaneous transluminal coronary angioplasty with a drug‐eluting stent within the previous year, severe congestive heart failure (New York Heart Association functional class III to IV), serum creatinine > 2 mg/dL, any condition limiting life expectancy < 2 years, and pregnancy or pre‐menopause.”
Interventions	Intervention: "aspirin (100 mg), simvastatin (40 mg), and ramipril at 3 different doses (2.5 mg, 5 mg, or 10 mg, which allowed for up‐titration at the discretion of the physician)” in hard‐shell gelatin capsule Comparator: aspirin, simvastatin, and ramipril provided separately Drugs were provided free of cost for both arms
Outcomes	Primary Medication adherence assessed by attendance at the final 9‐month visit and the MAQ and pill count methods, simultaneously. "Participants lost for follow‐up and those discontinuing medication due to adverse effects were also considered to be nonadherent for this analysis”. Definition: “Pill count was calculated as: (no. of pills dispensed – no. of pills returned)/number of pills prescribed X 100. A pill count between 80% and 110% was considered good adherence.” Blood pressure LDL cholesterol Secondary Incidence of adverse events including death, reinfarction, and rehospitalisation for any CV cause Rate of treatment withdrawal Tolerability Quality of life "Economic endpoints” Outcomes measured at 1, 4, and 9 months Follow‐up: 9 months
Notes	Comparator: individual drugs (aspirin, simvastatin, ramipril) provided separately
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"a central electronic randomization service assigned participants to 1 of 2 arms”
Allocation concealment (selection bias)	Low risk	“a central electronic randomization service assigned participants to 1 of 2 arms”
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open label trial
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Open label trial; no evidence of blinded outcome assessment committee
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Similar loss to follow‐up between groups (intervention 12.3%; comparator 10.1%, Table 2) but could influence primary outcome
Selective reporting (reporting bias)	Unclear risk	Primary outcome was reported, but the threshold for defining adherence was changed from 16‐20 during the trial. The effects of this change are uncertain. Data on 4‐month outcomes not reported but not likely different than longer term trends
Other bias	Unclear risk	Relatively small study to detect any differences in clinical outcomes; could be considered low risk of small study bias for adherence