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.