Table 1.
Results of Trials of DOACs for Stroke Prevention in NVAF.a
| RE-LY Dabigatran 110 mg BID46,49,50 | RE-LY Dabigatran 150 mg BID46,49,50 | ROCKET AF Rivaroxaban 20 mg QD48 | ENGAGE AF–TIMI 48 Edoxaban 30 mg QD45 | ENGAGE AF–TIMI 48 Edoxaban 60 mg QD45 | ARISTOTLE Apixaban 5 mg BID47 | AVERROES Apixaban 5 mg BID51 | |
|---|---|---|---|---|---|---|---|
| Comparator | Warfarin target INR, 2.0-3.0 | Warfarin target INR, 2.0-3.0 | Warfarin target INR, 2.0-3.0 | Warfarin target INR, 2.0-3.0 | Warfarin target INR, 2.0-3.0 | Warfarin target INR, 2.0-3.0 | Aspirin 80-324 mg |
| Total N | 18 113 | 14 264 | 21 105 | 18 201 | 5599 | ||
| Latin American patients (n) | 1134 (South America; ITT, both efficacy and safety) | 1878 (ITT); 1877 (SOT) | 2661 (ITT); 2651 (SOT) | 3468 (ITT); 3460 (SOT) | 1185 (ITT, efficacy and safety) | ||
| Efficacy | |||||||
| Stroke or systemic embolism (noninferiority) | 1.54 vs 1.71, RRR = 10%, P < .001 | 1.11 vs 1.71, RRR = 35%, P < .001 | PP: 1.7 vs 2.2, RRR = 21%, P < .001 | mITT: 1.61 vs 1.50, RRI = 7%, P = .005 | mITT:1.18 vs 1.50, RRR= 21%, P < .001 | 1.27 vs 1.60, RRR = 21%, P < .001 | |
| Stroke or systemic embolism (superiority) | 1.54 vs 1.72, RRR = 11%, P = .27 | 1.12 vs 1.72, RRR = 35%, P < .001 | 2.1 vs 2.4, RRR = 12%, P = .12, OT: 1.7 vs 2.2, RRR = 21%, P = .02 | 2.04 vs 1.80, RRI = 13%, P = .10 | 1.57 vs 1.80, RRR = 13%, P = .08 | 1.27 vs 1.60, RRR = 21%, P = .01 | 1.6 vs 3.7, RRR = 55%, P < .001 |
| Ischemic stroke | Ischemic or nonspecified 1.34 vs 1.22, RRI = 10%, P = .42 | Ischemic or nonspecified 0.93 vs 1.22, RRR = 24%, P = .03 | SOT: 1.34 vs 1.42, RRR = 6%, P = .581 | 1.77 vs 1.25, RRI = 41%, P < .001 | 1.25 vs 1.25, RRR = 0%, P = 0.97 | Ischemic or nonspecified, 0.97 vs 1.05, RRR = 8%, P = .42 | 1.1 vs 3.0, RRR = 63%, P < .001 |
| Hemorrhagic stroke | 0.12 vs 0.38, RRR = 69%, P < .001 | 0.10 vs 0.38, RRR = 74%, P < .001 | SOT: 0.26 vs 0.44, RRR: 41%, P =.024 | 0.16 vs 0.47, RRR = 67%, P < .001 | 0.26 vs 0.47, RRR = 46%, P < .001 | 0.24 vs 0.47, RRR = 49%, P < .001 | 0.2 vs 0.3, RRR = 33%, P = .45 |
| All-cause mortality | 3.75 vs 4.13, RRR = 9%, P = .13 | 3.64 vs 4.13, RRR = 12%, P = .051 | SOT: 1.87 vs 2.21, RRR = 15%, P = .073 | 3.80 vs 4.35, RRR = 13%, P =.006 | 3.99 vs 4.35, RRR = 8%, P = .08 | 3.52 vs 3.94, RRR = 11%, P = .047 | 3.5 vs 4.4, RRR = 21%, P = .07 |
| Safety | |||||||
| Major bleeding | 2.92 vs 3.61, RRR = 20%, P = .003 | 3.40 vs 3.61, RRR = 6%, P = .41 | SOT: 3.6 vs 3.4, RRI = 4%, P = .58 | SOT: 1.61 vs 3.43, RRR = 53%, P < .001 | SOT: 2.75 vs 3.43, RRR = 20%, P <.001 | SOT: 2.13 vs 3.09, RRR = 31%, P < .001 | 1.4 vs 1.2, RRI = 13%, P = .57, SOT: 1.4 vs 0.9, RRI = 54%, P = .07 |
| Intracranial hemorrhage | 0.23 vs 0.76, RRR = 70%, P < .001 | 0.32 vs 0.76, RRR = 59%, P < .001 | SOT: 0.5 vs 0.7, RRR = 33%, P = .02 | SOT: 0.26 vs 0.85, RRR = 70%, P < .001 | SOT: 0.39 vs 0.85, RRR = 53%, P < .001 | SOT: 0.33 vs 0.80, RRR = 58%, P < .001 | 0.4 vs 0.4, RRR = 15%, P = .69 |
Abbreviations: BID, twice daily; DOAC, direct oral anticoagulant; INR, international normalized ratio; ITT, intent to treat; mITT, modified intent to treat; NVAF, nonvalvular atrial fibrillation; OT, on treatment; PP, per protocol; QD, once daily; RRI, relative risk increase; RRR, relative risk reduction; SOT, safety on-treatment.
aBoth RRRs and RRIs are calculated from the published hazard ratios for ROCKET AF, ENGAGE AF–TIMI 48, ARISTOTLE, and AVERROES and from the published relative risks from RE-LY. All columns show DOAC versus warfarin, except AVERROES, which compared apixaban with aspirin. All data are presented as annual rates per 100 patients, except as noted. All analyses were performed on ITT populations unless otherwise specified. Adapted with permission of Dove Medical Press Ltd, from Foody JM. Clin Int Aging. 2017;12:175-187; permission conveyed through Copyright Clearance Center, Inc.