Table 2.
Phase III clinical trial results for the NOACs
| Comparator | RE-LY (dabigatran 110 mg)55
|
RE-LY (dabigatran 150 mg)55
|
ROCKET AF (rivaroxaban 20 mg)86
|
ARISTOTLE (apixaban 5 mg)56
|
AVERROES (apixaban 5 mg)57
|
ENGAGE AF-TIMI 48 (edoxaban 60 mg)58
|
ENGAGE AF-TIMI 48 (edoxaban 30 mg)58
|
|---|---|---|---|---|---|---|---|
| Warfarin | Warfarin | Warfarin | Warfarin | Aspirin | Warfarin | Warfarin | |
| Trial design | Randomized, open-label, rater-blinded, noninferiority trial | Randomized, open-label, rater-blinded, noninferiority trial | Randomized, double-dummy, double-blind, noninferiority trial | Randomized, double-dummy, double-blind, noninferiority trial | Randomized, double-dummy, double-blind, superiority trial | Randomized, double-dummy, double-blind, noninferiority trial | Randomized, double-dummy, double-blind, noninferiority trial |
| Stroke or systemic embolism | RR: 0.91 (95% CI: 0.74, 1.11); P=0.34* | RR: 0.65 (95% CI: 0.52, 0.81); P<0.001*,** | HR: 0.88 (95% CI: 0.75, 1.03); P=0.12a,* | HR: 0.79 (95% CI: 0.66, 0.95); P=0.01* | HR: 0.45 (95% CI: 0.32, 0.62); P<0.001** | HR: 0.79 (97.5% CI: 0.63, 0.99);b P<0.001* | HR: 1.07 (97.5% CI: 0.87, 1.31);b P=0.005* |
| Hemorrhagic stroke | RR: 0.31 (95% CI: 0.17, 0.56); P<0.001 | RR: 0.26 (95% CI: 0.14, 0.49); P<0.001 | HR: 0.59 (95% CI: 0.37, 0.93);c P=0.024 | HR: 0.51 (95% CI: 0.35, 0.75); P<0.001 | HR: 0.67 (95% CI: 0.24, 1.88); P=0.45 | HR: 0.54 (95% CI: 0.38, 0.77); P<0.001 | HR: 0.33 (95% CI: 0.22, 0.50); P<0.001 |
| Intracranial hemorrhage | RR: 0.30 (95% CI: 0.19, 0.45); P<0.001 | RR: 0.41 (95% CI: 0.28, 0.60); P<0.001 | HR: 0.67 (95% CI: 0.47, 0.93);c P=0.02 | HR: 0.42 (95% CI: 0.30, 0.58);c P<0.001 | HR: 0.69 (95% CI: 0.38, 1.90); P=0.69 | HR: 0.47 (95% CI: 0.34, 0.63);c P<0.001 | HR: 0.30 (95% CI: 0.21, 0.43);c P<0.001 |
| Myocardial infarction | RR: 1.29 (95% CI: 0.96, 1.75); P=0.09 | RR: 1.27 (95% CI: 0.94, 1.71); P=0.12 | HR: 0.81 (95% CI 0.63, 1.06);c P=0.121 | HR: 0.88 (95% CI: 0.66, 1.17); P=0.37 | HR: 0.86 (95% CI: 0.50, 1.48); P=0.59 | HR: 0.94 (95% CI: 0.74, 1.19); P=0.60 | HR: 1.19 (95% CI: 0.95, 1.49); P=0.13 |
| All-cause mortality | RR: 0.91 (95% CI: 0.80, 1.03); P=0.13 | RR: 0.88 (95% CI: 0.77, 1.00); P=0.051 | HR: 0.92 (95% CI: 0.82, 1.03); P=0.15 | HR: 0.89 (95% CI: 0.80, 0.998); P=0.047 | HR: 0.79 (0.62, 1.02); P=0.07 | HR: 0.92 (95% CI: 0.83, 1.01); P=0.08 | HR: 0.87 (95% CI: 0.79, 0.96); P=0.006 |
| Major bleeding | RR: 0.80 (95% CI: 0.70, 0.93); P=0.003 | RR: 0.93 (95% CI: 0.81, 1.07); P=0.32 | HR: 1.04 (95% CI: 0.90, 1.20);c P=0.58 | HR: 0.69 (95% CI: 0.60, 0.80);c P<0.001 | HR: 1.13 (95% CI: 0.74, 1.75); P=0.57 | HR: 0.80 (95% CI: 0.71, 0.91);c P<0.001 | HR: 0.47 (95% CI: 0.41, 0.55);c P<0.001 |
Notes: All values are for the intention-to-treat populations unless otherwise stated.
Noninferior to comparator;
superior to comparator;
the primary end point for ROCKET-AF used the per-protocol population. In the per-protocol analysis, the HR for stroke or systemic embolism with rivaroxaban vs 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.
Abbreviations: CI, confidence interval; HR, hazard ratio; NOAC, non-vitamin K antagonist oral anticoagulants; RR, relative risk; RE-LY AF, Randomized Evaluation of Long-Term Anticoagulation Therapy 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; ARISTOTLE, Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; AVERROES, Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment; ENGAGE AF-TIMI, Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation -Thrombolysis in Myocardial Infarction.