Clinically important properties of oral anticoagulants (OACs) with reference to phase III venous thromboembolism (VTE) treatment studies [30–34] and published pharmacology data [29, 35–39]
| Rivaroxaban (Xarelto; Bayer HealthCare/Janssen Pharmaceuticals) | Apixaban (Eliquis; Bristol-Myers Squibb/Pfizer) | Edoxaban (Lixiana; Daiichi Sankyo) | Dabigatran etexilate (Pradaxa; Boehringer Ingelheim) | Warfarin (generic) | |
| Mechanism of action | Direct factor Xa inhibitor | Direct factor Xa inhibitor | Direct factor Xa inhibitor | Direct thrombin inhibitor | Vitamin K antagonist |
| Currently approved for VTE treatment in Europe and the USA? | Yes | Yes | No | Yes | Yes |
| Time to maximum concentration h | 2–4 | 3–4 | 1–2 | 0.5–2 | Several days |
| Half-life h | 5–13 | ∼12 | 8–10 | 12–14 | ∼40 |
| Proportion of unchanged drug excreted renally % | 33# | 27 | 35 | 85 | Minor only |
| VTE treatment approach and dose | Single drug; 15 mg twice daily for 3 weeks, then 20 mg once daily | Single drug; 10 mg twice daily for 7 days, then 5 mg twice daily | Dual drug; after median 7 days of parenteral anticoagulation, 60 mg once daily | Dual drug; after 5–10 days of parenteral anticoagulation, 150 mg twice daily | Dual drug; start alongside parenteral anticoagulant, discontinue latter after ≥5 days when INR ≥2 for ≥2 days, adjust dose to maintain INR 2–3 |
| Dose adjustments for VTE treatment | None | No reduced dose tested in phase III trials | 30 mg once daily tested in patients with CrCl 30–50 mL·min−1 or body weight ≤60 kg or receiving concomitant strong P-gp inhibitors | No reduced dose tested in phase III trials | Frequent, guided by the INR |
| Incidence of clinically relevant/major bleeding in VTE treatment studies % | 10.3/1.1 (EINSTEIN PE) and 8.1/0.7 (EINSTEIN DVT) as a single drug | 4.3/0.6 (AMPLIFY) as a single drug | 8.5/1.4 (Hokusai-VTE) after parenteral induction | 5.6/1.6 (RE-COVER) after parenteral induction | Up to 11.4/2.2 in studies of direct OACs after parenteral induction |
| Reversal in bleeding emergency | PCC, aPCC or rFVIIa suggested for rivaroxaban, apixaban and dabigatran (specific antidotes in development) | PCC (vitamin K is slow) | |||
| Food effect | No interactions; take rivaroxaban 15 mg and 20 mg doses with food | No interaction; apixaban, edoxaban and dabigatran can be taken with or without food | Affected by many common foods, e.g. cranberry juice and vegetables containing high levels of vitamin K | ||
| Relevant drug interactions | Factor Xa inhibitors: strong inhibitors of CYP3A4 and P-gp: azole antimycotics (e.g. ketoconazole) and HIV protease inhibitors (e.g. ritonavir) | Dabigatran: strong P-gp inhibitors and inducers | Multiple | ||
Contraindicated/not recommended conditions are listed in table 3. INR: international normalised ratio; CrCl: creatinine clearance; P-gp: P-glycoprotein; PCC: prothrombin complex concentrate; aPCC: activated prothrombin complex concentrate; rFVIIa: recombinant activated factor VII; CYP3A4: cytochrome P450 3A4. #: 33% is also excreted renally as inactive metabolites.