Table 3.
Phase III clinical trial results for the novel oral anticoagulants
| RE-LY (dabigatran 110 mg)69,70 | RE-LY (dabigatran 150 mg)69,70 | ROCKET AF (rivaroxaban 20 mg)73 | ARISTOTLE (apixaban, 5 mg)72 | ENGAGE AF-TIMI 48 (edoxaban 60 mg)71 | ENGAGE AF-TIMI 48 (edoxaban, 30 mg)71 | |
|---|---|---|---|---|---|---|
| Stroke or systemic embolism | RR 0.90 (95% CI 0.74–1.10) | RR 0.65 (95% CI 0.52–0.81) | HR 0.88 (95% CI 0.75–1.03) | HR 0.79 (95% CI 0.66–0.95) | HR 0.79 (97.5% CI 0.63–0.99)b | HR 1.07 (97.5% CI 0.87–1.31)b |
| P<0.001 (noninferiority) | P<0.001 (noninferiority) | P<0.001 (noninferiority) | P<0.001 (noninferiority) | P<0.001 (noninferiority) | P=0.005 (noninferiority) | |
| P=0.30 | P<0.001 | P=0.12a | P=0.01 | P=0.08 | P=0.10 | |
| Hemorrhagic stroke | RR 0.31 (95% CI 0.17–0.56) | RR 0.26 (95% CI 0.14–0.49) | HR 0.59 (95% CI 0.37–0.93)c | HR 0.51 (95% CI 0.35–0.75) | HR 0.54 (95% CI 0.38–0.77) | HR 0.33 (95% CI 0.22–0.50) |
| P<0.001 | P<0.001 | P=0.024 | P<0.001 | P<0.001 | P<0.001 | |
| Intracranial hemorrhage | RR 0.30 (95% CI 0.19–0.45) | RR 0.41 (95% CI 0.28–0.60) | HR 0.67 (95% CI 0.47–0.93)c | HR 0.42 (95% CI 0.30–0.58)c | HR 0.47 (95% CI 0.34–0.63)c | HR 0.30 (95% CI 0.21–0.43)c |
| P<0.001 | P<0.001 | P=0.02 | P<0.001 | P<0.001 | P<0.001 | |
| Myocardial infarction | RR 1.29 (95% CI 0.96–1.75) | RR 1.27 (95% CI 0.94–1.71) | HR 0.81 (95% CI 0.63–1.06)c | HR 0.88 (95% CI 0.66–1.17) | HR 0.94 (95% CI 0.74–1.19) | HR 1.19 (95% CI 0.95–1.49) |
| P=0.09 | P=0.12 | P=0.121 | P=0.37 | P=0.60 | P=0.13 | |
| All-causemortality | RR 0.91 (95% CI 0.80–1.03) | RR 0.88 (95% CI 0.77–1.00) | HR 0.92 (95% CI 0.82–1.03) | HR 0.89 (95% CI 0.80–0.998) | HR 0.92 (95% CI 0.83–1.01) | HR 0.87 (95% CI 0.79–0.96) |
| P=0.13 | P=0.051 | P=0.15 | P=0.047 | P=0.08 | P=0.006 | |
| Major bleeding | RR 0.80 (95% CI 0.70–0.93) | RR 0.93 (95% CI 0.81–1.07) | HR 1.04 (95% CI 0.90–1.20)c | HR 0.69 (95% CI 0.60–0.80)c | HR 0.80 (95% CI 0.71–0.91)c | HR 0.47 (95% CI 0.41–0.55)c |
| P=0.003 | P=0.32 | P=0.58 | P<0.001 | P<0.001 | P<0.001 |
Notes:
The primary end point for ROCKET-AF used the per-protocol population. In the per-protocol analysis, the HR for stroke or SE with rivaroxaban versus warfarin was 0.79 (95% CI 0.66–0.96, P<0.001 for noninferiority);
modified intention-to-treat population in the treatment period;
safety on-treatment population. All values are for the intention-to-treat populations unless otherwise stated. All P-values are for superiority unless otherwise stated.
Abbreviations: CI, confidence interval; HR, hazard ratio; RR, relative risk; RE-LY, Randomized Evaluation of Long-term anticoagulant therapY; ARISTOTLE, Apixaban for Reduction In STroke and Other ThromboemboLic Events in atrial fibrillation; ROCKET AF, Rivaroxaban Once daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation; ENGAGE AF-TIMI 48, Effective aNticoaGulation with factor XA next GEneration in Atrial Fibrillation – Thrombolysis In Myocardial Infarction 48 study.