Table 4.
Rate of events [% patients/y, RR (95% CI), p value] for efficacy and safety endpoints in Phase III clinical trials comparing the effects of NOACs to warfarin.
| Dabigatran (RE-LY) [57] | Rivaroxaban (ROCKET-AF) [58] | Apixaban (ARISTOTLE) [59] | |||||
|---|---|---|---|---|---|---|---|
| Study design | Randomized, open-label | Randomized, double-blind | Randomized, double-blind | ||||
| Number of patients | 18,113 | 14,264 | 18,201 | ||||
| Groups | Dose-adjusted warfarin vs. blinded doses of dabigatran (150 mg b.i.d. or 110 mg b.i.d.) |
Dose-adjusted warfarin vs. rivaroxaban (20 mg q.d.) |
Dose-adjusted warfarin vs. apixaban (5 mg b.i.d.) |
||||
| W | D150 | D110 | W | R20 | W | A5 | |
| Incidence of stroke/systemic embolism | 1.72 | 1.12 [0.65 (0.52–0.81), p < 0.001 for noninferiority and superiority] | 1.54 [0.89 (0.73–1.09), p < 0.001 for noninferiority] | 2.4 | 2.1 [0.88 (0.75–1.03), p < 0.001 for noninferiority and p = 0.12 for superiority] | 1.6 | 1.27 [0.79 (0.66–0.95), p < 0.001 for noninferiority, p = 0.01 for superiority] |
| All-cause mortality | 4.13 | 3.64 [0.88 (0.77–1.00), p = 0.051] | 3.75 [0.91 (0.80–1.03), p = 0.13] | 2.21 | 1.87 [0.85 (0.70–1.02), p = 0.07] | 3.94 | 3.52 [0.89 (0.80–0.99), p = 0.047] |
| Major bleeding | 3.61 | 3.40 [0.94 (0.82–1.08), p = 0.41] | 2.92 [0.80 (0.70–0.93), p = 0.003] | 3.45 | 3.60 [1.04 (0.90–2.30), p = 0.58] | 3.09 | 2.13 [0.69 (0.60–0.80), p < 0.001] |
| Intracerebral hemorrhage | 0.77 | 0.32 [0.42 (0.29–0.61), p < 0.001] | 0.23 [0.29 (0.19–0.45), p < 0.001] | 0.74 | 0.49 [0.67 (0.47–0.93), p = 0.02] | 0.80 | 0.33 [0.42 (0.30–0.58), p < 0.001] |
| GI major bleeding | 1.09 | 1.60 [1.48 (1.19–1.86), p < 0.001] | 1.13 [1.04 (0.82–1.33), p = 0.74] | 1.24 | 2.00 [1.61 (1.30–1.99), p < 0.001] | 0.86 | 0.76 [0.89 (0.70–1.15), p = 0.37] |
Note. From “2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS,” by P. Kirchhof, S. Benussi, D. Kotecha, A. Ahlsson, D. Atar, B. Casadei, et al., 2016, Eur Heart J, 37, p. 2893–62. Copyright 2016, The European Society of Cardiology. Adapted with permission.
A5 = apixaban 5 mg b.i.d. = twice a day; CI = confidence interval; D150 = dabigatran 150 mg b.i.d.; D110 = dabigatran 110 mg b.i.d.; GI = gastrointestinal; NOACs = non-vitamin K antagonist oral anticoagulants; R20 = rivaroxaban 20 mg q.d. = once a day; RR = relative risk; W = warfarin.