Essence of this Article
Currently approved agents for the prevention of stroke in patients with atrial fibrillation (AF) include vitamin K antagonists (VKAs) and the novel oral anticoagulants (OACs) dabigatran, rivaroxaban, apixaban and edoxaban. VKAs, such as warfarin and acenocoumarol, are the most widely used medications for preventing thrombosis in patients with AF and, although they have proven benefit, they lack many properties of an ideal anticoagulant, such as rapid onset of action and predictable pharmacokinetics and pharmacodynamics. The novel OACs have many of these ideal properties and, therefore, have the potential to improve the quality of care. For this reason, the updated European Society of Cardiology (ESC) 2012 guidelines on the management of patients with AF recommend that novel OACs should be considered rather than adjusted-dose VKA (international normalized ratio [INR] 2.0–3.0) for most patients with non-valvular AF, based on their net clinical benefit.
Currently, the most widely used medications for preventing thrombosis in patients with AF are VKAs. These agents have proven efficacy but lack many of the properties of an ideal anticoagulant. Novel OACs that meet most of these criteria – having: a wide therapeutic window; the lack of a requirement for routine coagulation monitoring or frequent dose adjustments; predictable pharmacokinetics and pharmacodynamics; and low risk for drug–drug or drug–food interactions191 (resulting in more predictable anticoagulation) – have the potential to improve the quality of care. For these reasons, the European Society of Cardiology (ESC) 2012 guidelines on the management of AF recommend novel OACs rather than adjusted-dose VKAs (INR 2.0–3.0) for most patients with non-valvular AF, based on their net clinical benefit.187 Although the most recent American Heart Association/American College of Cardiology/Heart Rhythm Association (AHA/ACC/HRS) 2014 guidelines do not include a general recommendation for novel OACs over VKAs, it is recommended that patients unable to maintain a stable INR on VKA therapy are transitioned to a novel OAC.534
Approved agents for the prevention of stroke in patients with AF
|VKA192, 535, 536||Multiple coagulation factors||E.g. warfarin
Initial dose: typically 10 mg od for 2 days
typically 3–9 mg od (dose depends on the PT or other appropriate coagulation tests e.g. INR)
|Dabigatran||Thrombin (direct)||110 mg bid in patients with CrCl ≥30 ml/min
150 mg bid in patients with CrCl ≥30 ml/min
US only: 75 mg bid for patients with CrCl 15–30 ml/mina
Newly identified events in RE-LY194
Newly identified events in RE-LY537
|Rivaroxaban||Factor Xa (direct)||20 mg od
15 mg od for patients with moderate renal impairment (CrCl 30–49 ml/min) Patients with severe renal impairment (CrCl 15–29 ml/min) may also receive rivaroxaban 15 mg od, although caution must be appliedb
|Apixaban||Factor Xa (direct)||5 mg bid
2.5 mg bid for patients with ≥2 of the following criteria:
age ≥80 years;
body weight ≤60 kg;
serum creatinine ≥1.5 mg/dl
|Edoxaban||Factor Xa (direct)||60 mg od in patients with CrCl >50–≤95 ml/minc
30 mg od in patients with CrCl 15–50 ml/minb
|ENGAGE-AF TIMI 48538|
|NB. Differences in design, patient populations, blinding and statistical powering of the trials preclude direct comparison between these trials.
a The EU label for dabigatran states that its use is contraindicated in patients with CrCl <30 ml/min; buse is not recommended in patients with CrCl <15 ml/min; cedoxaban 60 mg od should not be used in patients with CrCl >95 ml/min because of an increased risk of ischaemic stroke compared with warfarin (hazard ratio 2.16; 95% confidence interval 1.17–3.97).
bid, twice daily; CrCl, creatinine clearance; INR, international normalized ratio; od, once daily; PT, prothrombin time; US, United States; VKA, vitamin K antagonist.