Table 2. Pivotal trials for new oral anticoagulants.
| Drug | Dabigatran (pradaxa™) |
Rivaroxaban (xarelto™) |
Apixaban (eliquis™) |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 6,076, NOAC† (%/yr) | 6,022, Warf (%/yr) | RR (95% CI) | P value | 7,081, NOAC†,‡ | 7,090, Warf‡ | HR (95% CI) | P value | 9,120, NOAC† (%/yr) | 9,081, Warf (%/yr) | HR (95% CI) | P value | |||
| Drug trial | RE-LY | ROCKET-AF | ARISTOTLE | |||||||||||
| Study design and analysis | Multicenter, open-label, intent-to-treat | Multicenter, double-blind, per protocol | Multicenter, double-blind, intent-to-treat | |||||||||||
| No. in sample | 18,153 | 14,264 | 18,201 | |||||||||||
| Efficacy | ||||||||||||||
| SSE | 1.11 | 1.69 | 0.66 (0.74-1.11) | <0.001* | 2.1 | 2.4 | 0.88 (0.75-1.03) | <0.001* | 1.27 | 1.6 | 0.79 (0.66-0.95) | 0.01 | ||
| Stroke (all) | 1.01 | 1.57 | 0.64 (0.51-0.81) | <0.001 | 1.65 | 1.96 | 0.85 (0.70-1.03) | 0.092 | 1.19 | 1.51 | 0.79 (0.65-0.95) | 0.01 | ||
| Hemorrhagic | 0.1 | 0.38 | 0.26 (0.14-0.49) | <0.001 | 0.26 | 0.44 | 0.59 (0.37-0.93) | 0.024 | 0.24 | 0.47 | 0.51 (0.35-0.75) | <0.001 | ||
| Ischemic or NOS | 0.92 | 1.2 | 0.76 (0.60-0.98) | 0.03 | 1.34 | 1.42 | 0.94 (0.75-1.17) | 0.581 | 0.97 | 1.05 | 0.92 (0.74-1.13) | 0.42 | ||
| Disabling | 0.66 | 1 | 0.66 (0.50-0.88) | 0.005 | 0.39 | 0.5 | 0.77 (0.52-1.14) | 0.188 | ||||||
| Non-disabling | 0.37 | 0.58 | 0.62 (0.43-0.91) | 0.01 | 0.79 | 0.77 | 1.03 (0.76-1.38) | 0.863 | ||||||
| MI | 0.74 | 0.53 | 1.38 (1.00-1.91) | 0.048 | 0.91 | 1.12 | 0.81 (0.63-1.06) | 0.121 | 0.53 | 0.61 | 0.88 (0.66-1.17) | 0.37 | ||
| PE | 0.15 | 0.09 | 1.61 (0.76-3.42) | 0.21 | ||||||||||
| All-cause mortality | 3.64 | 4.13 | 0.88 (0.77-1.00) | 0.051 | 1.87 | 2.21 | 0.85 (0.70-1.02) | 0.073 | 3.52 | 3.94 | 0.89 (0.80-0.998) | 0.047 | ||
| Safety | ||||||||||||||
| Major bleed | 3.11 | 3.36 | 0.93 (0.81-1.07) | 0.31 | 3.6 | 3.4 | 1.04 (0.90-1.20) | 0.58 | 2.13 | 3.09 | 0.69 (0.60-0.80) | <0.001 | ||
| Fatal bleed | 1.45 | 1.8 | 0.81 (0.66-0.99) | 0.04 | 0.2 | 0.5 | 0.50 (0.31-0.79) | 0.003 | ||||||
| ICH hemorrhage | 0.3 | 0.74 | 0.40 (0.27-0.60) | <0.001 | 0.5 | 0.7 | 0.67 (0.47-0.93) | 0.02 | 0.33 | 0.8 | 0.42 (0.30-0.58) | <0.001 | ||
| Any bleed | 16.42 | 18.15 | 0.91 (0.86-0.97) | 0.002 | 14.9 | 14.5 | 1.03 (0.96-1.11) | 0.44 | 18.1 | 25.8 | 0.71 (0.68-0.75) | <0.001 | ||
NOAC, new oral anticoagulant; Warf, warfarin; RR, relative risk; HR, hazard ratio; SSE, stroke or systemic embolism; MI, myocardial infarction; PE, pulmonary embolism; ICH, intracranial hemorrhage. *, indicates analysis for noninferiority; †, analysis shown only for high doses formulations of anticoagulants; ‡, event/100 patient-yr; §, bleeding was defined as: RE-LY, reduction of hemoglobin level of at least 20 g/L, transfusion of at least 2 units of packed red blood cells, symptomatic bleeding in a critical area or organ; ROCKET-AF, reduction of hemoglobin of at least 2 g/dL, transfusion of at least 2 units of packed red blood cells, overt bleeding involving a critical anatomical site (intracranial, spinal, ocular, pericardial, articular, retroperitoneal, intramuscular with compartment syndrome) permanent disability, fatal outcome; ARISTOTLE, acute or sub-acute clinically overt bleeding accompanied by at least one of the following: decrease in hemoglobin level of at least 2 g/dL, bleed requiring transfusion of at least 2 units of packed red blood cells, or bleeding that was fatal or occurred in a critical site (intracranial, spinal, ocular, pericardial, articular, intramuscular with compartment syndrome, retroperitoneal).