For low-risk patients with atrial fibrillation, aspirin, or no treatment, may be sufficient. For higher-risk patients, treatment options include warfarin, aspirin and clopidogrel. Several studies have compared the efficacy of antiplatelet regimens to warfarin.9-11 The Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study showed that warfarin (target INR 2–3) was superior to aspirin 75 mg daily.10 The ACTIVE-W trial showed that clopidogrel plus aspirin was associated with a 45% increase in the risk of stroke, non-central nervous system embolism, myocardial infarction or vascular death compared to oral anticoagulation (annual rates for events 5.60% vs 3.93% respectively, p=0.0002). However, the cumulative risk of major bleeding complications was nearly identical (2.4% vs 2.2% per year, p=0.67).11 In summary, warfarin is more effective in preventing cerebrovascular events than dual antiplatelet therapy, although the danger of major bleeding is similar.11
The INR is usually maintained between 2 and 3,12 but a higher range may be appropriate in patients with prosthetic heart valves or rheumatic mitral valve disease. In patients unable to take warfarin, adding clopidogrel to aspirin reduces the risk of major vascular events by 11%, particularly stroke, but increases the risk of major haemorrhage by 57%.13
Fig. 2
Proposed management of non-valvular atrial fibrillation
Alternative oral anticoagulants
Several effective substitutes for warfarin are used for stroke prevention in North America and Europe. These include the direct thrombin antagonist dabigatran and factor Xa inhibitors such as rivaroxaban, apixaban, betrixaban and edoxaban.14
Dabigatran is the first drug to show non-inferiority to warfarin for stroke prevention in atrial fibrillation.4,14-16 The 150 mg twice-daily dose was superior to warfarin in efficacy with a similar risk of major bleeding whereas 110 mg twice daily was non-inferior for efficacy with a reduced risk of major bleeding. The risk of intracranial haemorrhage was less with both doses of dabigatran than with warfarin.15-18 Rivaroxaban is also an effective anticoagulant.19,20 The main advantage of rivaroxaban and dabigatran over warfarin is they have more predictable pharmacokinetics, and routine anticoagulation monitoring is not needed. No interaction between cytochrome P450 enzymes and dabigatran has been observed, although P-glycoprotein inhibitors such as amiodarone and verapamil may increase plasma concentrations of dabigatran and lead to an increased bleeding risk. There is also a risk of dabigatran accumulation in renal impairment.14 There is no antidote if bleeding occurs with dabigatran and rivaroxaban.
These drugs may replace warfarin for thromboembolic prophylaxis in atrial fibrillation if their cost-effectiveness can be shown.21 However, for a condition that requires long-term prophylaxis there are no long-term data to suggest that they will be safe and effective alternatives.