RE‐LY Study 2009.

Methods	Study design: parallel RCT Study duration: 22 December 2005 to 15 March 2009 Median duration of study follow‐up: 2.0 years
Participants	Country: Taiwan, Colombia, Mexico, Peru, Romania, India, Russia, Brazil, China, Korea, Greece, Thailand, Malaysia, Poland, Japan, South Africa, France, Slovakia, Portugal, Israel, Czech Republic, Philippines, Bulgaria, Hungary, Hong Kong, Turkey, Belgium, Austria, USA, Spain, Germany, Switzerland, Singapore, Argentina, Netherlands, Norway, Canada, Italy, Ukraine, UK, Denmark, Australia, Finland, Sweden Setting: multicentre Relevant health status: participants with non‐valvular AF, moderate kidney impairment (30 ≤ CrCl < 50 mL/min); aged ≥ 18 years, and at least one of the following risk factors for stroke; previous stroke or TIA, a left ventricular ejection fraction of less than 40%, New York Heart Association class II or higher heart‐failure symptoms within 6 months before screening, and an age of at least 75 years or an age of 65 to 74 years plus DM, hypertension, or coronary artery disease Number: treatment group (2428); control group (1126) Mean age ± SD: 75.2 ± 7.2 years Sex (M/F): 1803/1571 Exclusion criteria: presence of a severe heart‐valve disorder; stroke within 14 days or severe stroke within 6 months before screening; a condition that increased the risk of haemorrhage; CrCl < 30 mL/min; active liver disease; pregnancy
Interventions	Treatment group Oral dabigatran: 110 mg or 150 mg twice daily Control group Oral warfarin: dose‐adjusted (target INR 2.0 to 3.0)
Outcomes	All strokes and systemic embolic events All‐cause mortality Major bleeding (not included in this review because of the result from conventional ITT analysis) Intracranial haemorrhage (not included in this review because of the result from conventional ITT analysis)
Notes	Funding source: Boehringer Ingelheim Pharmaceuticals
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomly assigned to treatment groups with means of a central, interactive, automated telephone system
Allocation concealment (selection bias)	Low risk	Allocation was concealed because participants were assigned to each group using a central, interactive, automated telephone system
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Dabigatran was administered in a blinded fashion, but warfarin was administered in an unblinded fashion. But we judged that incomplete blinding didn't give influence for the outcomes, because the outcomes were objective measures and the outcome assessors were blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Each primary and secondary outcome event was adjudicated by two independent investigators who were unaware of the treatment assignments
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	All outcomes were analyses in the ITT population. The information about discontinuation during study was unclear
Selective reporting (reporting bias)	Low risk	All predefined efficacy and safety outcomes were reported
Other bias	High risk	The study was funded by Boehringer Ingelheim Pharmaceuticals