Table 1.
Characteristics of the studies that investigated the efficacy of DOAC compared to VKA for treatment of VTE.
| Study | Einstein DVT + PE | AMPLIFY | RE-COVER I + II | Hokusai-VTE |
|---|---|---|---|---|
| Drug | Rivaroxaban | Apixaban | Dabigatran | Edoxaban |
| Total number of patients | 8246 | 5365 | 5107 | 8240 |
| Target | Factor Xa-inhibition | Factor Xa-inhibition | Thrombin-inhibition | Factor Xa-inhibition |
| Primary efficacy outcome | Recurrent venous thromboembolism | |||
| Principal safety outcome | Major- or clinically relevant non-major bleeding | |||
| Study design | Open-label, randomized non-inferiority trial | Randomized, double-blind trial | Randomized, double-blind, non-inferiority trial | Randomized, double-blind, non-inferiority trial |
| Time INR in therapeutic rangea | 57.7% | 61% | 60% | 63.5% |
| Regimen/dose (mg) | 15 mg twice daily for the first 3 weeks followed by 20 mg once daily | 10 mg twice daily for the first 7 days, followed by 5 mg twice daily | Initial treatment (at least 5 days) with parenteral anticoagulant, followed by 150 mg twice daily | Initial treatment (at least 5 days) with parenteral anticoagulant, followed by 60 mg once daily |
| Treatment duration | 3-, 6-, and 12 months | 6 months | 6 months | 3–12 months duration determined by the treating physician based on patient’s clinical features and preference |
| Dose adjustment | No | No | No | Yesb |
| Dose reduction criteria | Not assessed | Not assessed | Not assessed | 30 mg once daily in patients with a CrCl 30–50 mL/min, body weight ≤60 kg or concomitant treatment with potent P-glycoprotein inhibitor |
| Most important exclusion criteria as listed in the publications (full list of exclusion criteria provided in the study protocols) | Another indication for VKA, CrCl <30 mL/min, liver disease, bacterial endocarditis, contraindications for anticoagulant treatment, systolic blood pressure >180 mmHg or diastolic blood pressure >110, childbearing potential without proper contraceptive measures, pregnancy or breast feeding, concomitant use of strong cytochrome P450 3A4 inhibitors, bacterial endocarditis | Contraindications to heparin or warfarin, CrCl <25 mL/min or creatinine level >2.5 mg/dL, liver disease, cancer with long-term treatment with LMWH, provoked DVT or PE in the absence of a persistent risk factor for recurrence, another indication for long-term anticoagulation therapy, dual antiplatelet therapy, aspirin at a dose of more than 165 mg daily, hemoglobin <9 mg/dL, platelet count <100.000/mm3 | Another indication for a VKA or heparin, CrCl <30 mL/min, liver disease, PE with hemodynamic instability or requiring thrombolytic therapy, recent unstable cardiovascular disease, high risk of bleeding, liver disease, contraindication to heparin, pregnancy or risk of becoming pregnant long-term antiplatelet therapy (aspirin ≤100 mg accepted), life expectancy less than 6 months | Another indication for VKA, CrCl <30 mL/min, contraindications to heparin or warfarin, cancer with long-term treatment with LMWH, treatment with aspirin at a dose of more than 100 mg daily or dual antiplatelet therapy |
aTarget INR (vitamin K antagonist) in all studies: 2.0–3.0.
CrCL, creatinine clearance; VKA, vitamin K antagonist; LMWH, low molecular weight heparin; DVT, deep vein thrombosis; PE, pulmonary embolism.
bIn the Hokusai-VTE study, 17.8% of patients received the adjusted dose of edoxaban (30 mg once daily) at randomization.