IMPACT 2014.

Methods	"Open label randomised control trial"
Participants	513 participants (from 91 General Practitioners); target = 600 participants in New Zealand 256 polypill; 257 comparator Mean (SD) age: 62 (8) years for both arms Maori ethnicity: 50% for both arms Women: 39% intervention; 34% comparator CAD: 35% intervention; 38% comparator DM: 44% intervention; 41% comparator Employed: 46% intervention; 44% comparator “Given the available funding resources, the recruitment target was revised down to 500, which provided 89‐93% power to detect the same differences between risk factors and 92% power to detect a 30% relative improvement in adherence.” Inclusion criteria: "Adults aged 18‐79 years at high risk of cardiovascular disease (based on either established disease (coronary, cerebrovascular, or peripheral vascular) or ≥15% five year risk of a cardiovascular event); patient’s general practitioner considered all the drugs in at least one of the two versions of the fixed‐dose combination treatment available were recommended and was uncertain if treatment was best provided as fixed‐dose combination based treatment or as usual care" Exclusion criteria: "contraindications to any of the components of the fixed dose combination, congestive heart failure, haemorrhagic stroke, active stomach or duodenal ulcer, receipt of an oral anticoagulant, concerns by the general practitioner about the risk to a patient of changing his or her cardiovascular disease drugs, impending alteration of a drug regimen for an important length of time (for example, planned coronary bypass graft operation), or the participant was unlikely to complete the trial or trial procedures"
Interventions	Intervention: Aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg, atenolol 50 mg or Aspirin 75 mg, simvastatin 40 mg, and lisinopril 10 mg, hydrochlorothiazide 12.5 mg Comparator: "The control is usual management. Physicians in both groups are encouraged to prescribe in line with New Zealand CVD risk assessment and management guidelines.” "both trial drugs and usual drugs were dispensed through community pharmacies." "Participants were required to pay what they would normally pay to receive a single government subsidised drug" "Standard patient co‐payments of NZ$5 (£2.6; €3.1; $4.3) for each item every three months"
Outcomes	Primary: Adherence (self‐reported current use of antiplatelet, statin, and at least two blood pressure‐lowering drugs) at 12 months Change in blood pressure between baseline and 12 months Change in LDL‐C between baseline and 12 months Secondary: Serious adverse events Cardiovascular events Health‐related quality of life (EuroQol EQ‐5D) Outcomes measured: baseline, 1, 6, 12 months, end of trial Follow‐up: median of 23 months in both arms
Notes	Comparator: usual care
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	“A central randomisation service randomly assigned (1:1) participants to fixed dose combination based treatment or usual care.”
Allocation concealment (selection bias)	Low risk	“A central randomisation service randomly assigned (1:1) participants to fixed dose combination based treatment or usual care.”
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open label trial
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Adherence: self‐report but corroborated by pharmacy claims data but definition favours intervention (requiring second BP lowering drug, though sensitivity analyses showed similar direction of effect) LDL/SBP objectively measured and not likely too susceptible to bias SAE/CV events self‐reported but objective and reviewed by endpoints committee
Incomplete outcome data (attrition bias) All outcomes	Low risk	Loss to follow‐up rates low and balanced
Selective reporting (reporting bias)	Low risk	Outcome reporting largely matches protocol; 6‐month data may not have been reported but not likely different than longer term outcome trends
Other bias	Unclear risk	Small study bias to evaluate differences in clinical outcomes