Table 3. Pivotal trials for novel oral anticoagulants.
| Drug | Apixaban (ELIQUISTM) | Edoxaban (SAVAYSATM) | ||||||
|---|---|---|---|---|---|---|---|---|
| Drug trial | AMPLIFY | HOKUSAI VTE | ||||||
| Study design | Multicenter, double-blind, intent-to-treat | Multicenter, double-blind, modified intent-to-treat | ||||||
| No. in sample | 2,609 | 2,635 | − | − | 4,118 | 4,122 | − | − |
| Sample size per cohort | NOAC | Enoxaparin/warfarin | RR (95% CI) | P value | NOAC | Warfarin | HR (95% CI) | P value |
| Efficacy | ||||||||
| VTE or VTE related death | 2.3% | 2.7% | 0.84 (0.60–1.18) | <0.001* | 3.2% | 3.5% | 0.89 (0.70–1.13) | <0.001* |
| DVT | 0.8% | 1.3% | − | − | 1.4% | 1.5% | − | − |
| Nonfatal PE | 1.0% | 0.9% | − | − | 1.2% | 1.4% | − | − |
| Fatal PE | <0.1% | 0.1% | − | − | 0.1% | 0.1% | − | − |
| ACM | 1.5% | 1.9% | 0.79 (0.53–1.19) | − | 3.2% | 3.1% | − | − |
| VTE or death from any cause | 3.2% | 3.9% | 0.82 (0.61–1.08) | 0.16 | 5.5% | 5.5% | 1.00 (0.83–1.20) | 1.00† |
| Safety | ||||||||
| Major bleeding | 0.6% | 1.8% | 0.31 (0.17–0.55) | <0.001† | 1.4% | 1.6% | 0.84 (0.59–1.21) | 0.35† |
| Non-major bleeding | 3.8% | 8.0% | 0.48 (0.38–0.60) | − | 7.2% | 8.9% | 0.80 (0.68–0.93) | 0.004† |
| Major + non-major bleeding | 4.3% | 9.7% | 0.44 (0.36–0.55) | <0.001 | 8.5% | 10.3% | 0.81 (0.71–0.94) | 0.004† |
*, 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.