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. 2016 Dec;6(6):570–581. doi: 10.21037/cdt.2016.11.17

Table 2. Pivotal trials for novel oral anticoagulants.

Drug Dabigatran (PRADAXATM) Rivaroxaban (XARELTOTM)
Drug trial RE-COVER (RI), RE-COVER II (RII) EINSTEIN DVT (EDVT), EINSTEIN PE (EPE)
Study design Multicenter, double-blind, intent-to-treat Multicenter, double-blind
No. in sample I: 1,274; II: 1,279 I: 1,265; II: 1,289 DVT: 1,731; PE: 2,419 DVT: 1,718; PE: 2,413
Sample size per cohort NOAC Warfarin HR (95% CI) P value NOAC Warfarin HR (95% CI) P value
Efficacy
   Recurrent VTE or VTE related death 2.4% (RI) 2.1% (RI) 1.10 (0.65–1.84) (RI) 2.1% (EDVT) 3.0% (EDVT) 0.68 (0.44–1.04) <0.001
2.7% (RII) 2.3% (RII) 1.13 (0.69–1.85) (RII) 2.1% (EPE) 1.8% (EPE) 1.12 (0.75–1.68) 0.003
   DVT 1.3% (RI) 1.4% (RI) 0.87 (0.44–1.71) (RI) 0.8% (EDVT) 1.6% (EDVT)
2.0% (RII) 1.3% (RII) 1.48 (0.80–2.74) (RII) 0.7% (EPE) 0.7% (EPE)
   Non-fatal PE 1.0% (RI) 0.6% (RI), 1.85 (0.74–4.64) (RI) 1.2% (EDVT) 1.0% (EDVT)
0.5% (RII) 1.0% (RII) 0.54 (0.21–1.35) (RII) 0.9% (EPE) 0.8% (EPE)
   Fatal PE 0.1% (RI) 0.2% (RI) 0.33 (0.03–3.15) (RI) <0.1% (EDVT) 0.0% (EDVT)
0.2% (RII) 0.0% (RII) 0.1% (EPE) <0.1% (EPE)
   ACM 1.6% (RI) 1.7% (RI) 0.98 (0.53–1.79) (RI) 2.2% (EDVT) 2.9% (EDVT) 0.67 (0.44–1.02) 0.06
2.0% (RII) 1.9% (RII) 0.98 (0.56–1.71) (RII) 2.4% (EPE) 2.1% (EPE) 1.13 (0.77–1.65) 0.53
Safety
   Major bleeding 1.6% (RI) 1.9% (RI), 0.82 (0.45–1.48) (RI) 0.8% (EDVT) 1.2% (EDVT) 0.65 (0.33–1.30) 0.21
1.2% (RII) 1.7%(RII) 0.69 (0.36–1.32) (RII) 1.1% (EPE) 2.2% (EPE) 0.49 (0.31–0.79) 0.003
   Non-major bleeding 7.3% (EDVT) 7.0% (EDVT)
9.5% (EPE) 9.8% (EPE)
   Major + non-major bleeding 5.6% (RI) 8.8% (RI) 0.63 (0.47–0.84) (RI) 8.1% (EDVT) 8.1% (EDVT) 0.97 (0.76–1.22) 0.77
5.0% (RII) 7.9% (RII) 0.62 (0.45–0.84) (RII) 10.3% (EPE) 11.4% (EPE) 0.90 (0.76–1.07) 0.23

*, indicates analysis for noninferiority; , indicates analysis for superiority; , presented data includes additional 30-day follow-up outcomes; §, major bleeding was defined as: RE-COVER, RE-COVER II, EINSTEIN DVT, EINSTEIN PE, AMPLIFY, HOKUSAI VTE, if it was clinically overt and if it was associated with a fall in the hemoglobin level of at least 20 g per liter, resulted in the need for transfusion of 2 or more units of red cells, involved a critical site, or was fatal; , clinically relevant non-major bleeding was defined as: RE-COVER, RE-COVER II, AMPLIFY, HOKUSAI VTE, at least one of the following: spontaneous skin hematoma of at least 25 cm2, spontaneous nosebleed more than 5 minutes duration, macroscopic hematuria, spontaneous rectal bleeding, gingival bleeding for more than 5 minutes, bleeding leading to hospitalization and/or surgical treatment, bleeding leading to a transfusion of less than 2 units of whole blood or red cells, any other bleeding considered clinically relevant by the investigator; EINSTEIN DVT, EINSTEIN PE, overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, unscheduled contact with a physician, interruption or discontinuation of study treatment, or associated with any other discomfort such as pain or impairment of activities of daily life. NOAC, new oral anticoagulant; RR, relative risk; HR, hazard ratio; DVT, deep venous thrombosis; PE, pulmonary embolism; EDVT, Einstein DVT Trial; EPE, Einstein PE Trial; ACM, all cause mortality.