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  actionDirect factor Xa inhibitorDirect factor Xa inhibitorDirect factor Xa inhibitorDirect thrombin inhibitorVitamin K antagonist
Currently  approved for VTE  treatment in Europe  and the USA?YesYesNoYesYes
Time to maximum  concentration h2–43–41–20.5–2Several days
Half-life h5–13∼128–1012–14∼40
Proportion of  unchanged drug  excreted renally %33#273585Minor only
VTE treatment  approach and doseSingle drug; 15 mg twice daily for 3 weeks, then 20 mg once dailySingle drug; 10 mg twice daily for 7 days, then 5 mg twice dailyDual drug; after median 7 days of parenteral anticoagulation, 60 mg once dailyDual drug; after 5–10 days of parenteral anticoagulation, 150 mg twice dailyDual 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 treatmentNoneNo reduced dose tested in phase III trials30 mg once daily tested in patients with CrCl 30–50 mL·min−1 or body weight ≤60 kg or receiving concomitant strong P-gp inhibitorsNo reduced dose tested in phase III trialsFrequent, 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 drug4.3/0.6 (AMPLIFY) as a single drug8.5/1.4 (Hokusai-VTE) after parenteral induction5.6/1.6 (RE-COVER) after parenteral inductionUp to 11.4/2.2 in studies of direct OACs after parenteral induction
Reversal in bleeding  emergencyPCC, aPCC or rFVIIa suggested for rivaroxaban, apixaban and dabigatran (specific antidotes in development)PCC (vitamin K is slow)
Food effectNo interactions; take rivaroxaban 15 mg and 20 mg doses with foodNo interaction; apixaban, edoxaban and dabigatran can be taken with or without foodAffected by many common foods, e.g. cranberry juice and vegetables containing high levels of vitamin K
Relevant drug  interactionsFactor 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 inducersMultiple
  • 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.