Direct-acting oral anticoagulants to prevent thromboembolic events in atrial fibrillation
Direct-acting oral anticoagulants (DOACs) include factor Xa inhibitors (eg apixaban, rivaroxaban) and direct thrombin inhibitors (eg dabigatran). In clinical trials of DOACs for patients with atrial fibrillation, DOACs were at least noninferior to warfarin for preventing thromboembolism and stroke. In the clinical trials, all the DOACs had significantly lower rates of intracranial bleeding and haemorrhagic stroke than warfarin. The rates of major bleeding overall with dabigatran and rivaroxaban were similar to warfarin, and the rate of major bleeding with apixaban was significantly lower than with warfarinConnolly, 2009Giugliano, 2013Granger, 2011Patel, Mahaffey, Garg, Pan, Singer, Hacke, Breithardt, Halperin, Hankey, Piccini, Becker, Nessel, Paolini, Berkowitz, Fox, Califf, , 2011.
Based on the comparable efficacy and lower risk of intracranial haemorrhage, DOACs are preferred over warfarin in most patients with atrial fibrillation who require anticoagulation1. The exception is in patients with rheumatic mitral stenosis and/or a mechanical heart valve, when warfarin is recommended. Warfarin may also be preferred over a DOAC in patients with concomitant severe kidney impairment or another indication for warfarin therapy (eg antiphospholipid syndrome)Steffel, 2021.
Comparison between the different DOACs is difficult because apixaban, rivaroxaban and dabigatran have all been trialled against warfarin but not against each otherConnolly, 2009Eikelboom, 2013Granger, 2011Patel, Mahaffey, Garg, Pan, Singer, Hacke, Breithardt, Halperin, Hankey, Piccini, Becker, Nessel, Paolini, Berkowitz, Fox, Califf, , 2011.
DOACs have a predictable dose response and do not need routine anticoagulation monitoring. Follow DOAC dosage recommendations for atrial fibrillation exactly; underdosing can reduce the effectiveness of stroke prevention, and overdosing can increase the bleeding risk. Before using DOACs for long-term therapy, weigh up the harm–benefit balance (ie the risk of bleeding versus the risk of thromboembolism and stroke)—see Stroke and bleeding risk assessment for atrial fibrillation.
To prevent thromboembolic events with apixaban for a patient with atrial fibrillation, use:
apixaban apixaban apixaban apixaban
patient with at least 2 risk factors for bleeding (ie age 80 years or older, weight 60 kg or less, and serum creatinine 133 micromol/L or more): 2.5 mg orally, twice daily
all other patients: 5 mg orally, twice daily.
Do not use apixaban if calculated creatinine clearance (CrCl) is less than 25 mL/min.
See Practical information on using apixaban for further information, including management of bleeding.
To prevent thromboembolic events with rivaroxaban for a patient with atrial fibrillation, use:
rivaroxaban rivaroxaban rivaroxaban rivaroxaban
CrCl 50 mL/min or more: 20 mg orally, once daily
CrCl 15 to 49 mL/min: 15 mg orally, once daily.
Do not use rivaroxaban if calculated CrCl is less than 15 mL/min. At the time of writing, data are limited for the use of rivaroxaban in patients with atrial fibrillation who have a CrCl of 15 to 29 mL/min; consider its use in these patients under specialist adviceColeman, 2019Lin, 2021Weir, 2020.
See Practical information on using rivaroxaban for further information, including management of bleeding.
To prevent thromboembolic events with dabigatran for a patient with atrial fibrillation, use:
dabigatran dabigatran dabigatran dabigatran
younger than 75 years and CrCl more than 50 mL/min: 150 mg orally, twice daily
younger than 75 years and CrCl 30 to 50 mL/min, or increased risk of major bleeding: 110 mg orally, twice daily
75 years or older and CrCl more than 30 mL/min: 110 mg orally, twice daily.
Do not use dabigatran if calculated CrCl is less than 30 mL/min.
See Practical information on using dabigatran for further information, including management of bleeding.
If using a DOAC in a patient with obesity, see also Anticoagulation to prevent thromboembolic events in patients with atrial fibrillation and obesity.