Drug, trial Dabigatran RE-LY [22 , 48 ] Rivaroxaban ROCKET [23 , 49 ] Apixaban ARISTOTLE [24 , 50 ] No. in sample 18113 14264 18201 Treatment characteristics Experimental drug Dabigatran 150 mg or 110 mg twice daily Rivaroxaban 20 mg or 15 mg once daily Apixaban 5 mg or 2.5 mg twice daily Experimental,
12091 7131 9120 High-dose 6076 5624 8702 Low-dose 6015 1597 428 Control drug Warfarin dose-adjusted to INR 2-3, once daily Warfarin dose-adjusted to INR 2-3, once daily Warfarin dose-adjusted to INR 2-3, once daily Control,
6022 7133 9081 TTR (%) Mean 64.4 55.2 62.2 Median 67 58 66 Trial phase III III III Design of randomised controlled trial Multicentre, open-label Multicentre, double-blind Multicentre, double-blind Adjudicating committee and blinded adjudication of outcomes Yes Yes Yes Interim analysis,
2 1 1 Number of exclusion criteria 14 31 19 Main efficacy outcome Stroke and SEE Stroke and SEE Stroke and SEE Main analysis Non-inferiority Non-inferiority Non-inferiority Non-inferiority margin Relative risk < 1.46 Relative risk < 1.46 Relative risk < 1.38 Main population of analysis Intent-to-treat Per protocol Intent-to-treat Main period of analysis Until notification of study termination On-treatment plus 2 days Until notification of study termination Main safety outcome Major bleeding Clinically relevant bleeding Major bleeding Main population of analysis Safety population Safety population Safety population Main period of analysis On-treatment plus 6 days* On-treatment plus 2 days* On-treatment plus 2 days* Jadad Score 3 5 5 Median length follow-up (days) 730 707 657
