Apixaban and atrial fibrillation: no clear advantage

For the prevention of thromboembolic events in patients with atrial fibrillation and a high thrombotic risk, the standard treatment is warfarin, an anticoagulant. Dabigatran, a thrombin inhibitor, is the alternative when warfarin fails to maintain the INR within the therapeutic range. Patients with a moderate thrombotic risk may receive either warfarin or low-dose aspirin. Apixaban, a factor Xa inhibitor anticoagulant, has been authorised in the European Union for use in patients with non-valvular atrial fibrillation and a moderate or high risk of thrombosis. In a double-blind, randomised non-inferiority trial versus warfarin in 18 201 patients, the incidence of stroke or systemic embolism was lower in the apixaban group (average 1.3 versus 1.6 events per 100 patient-years; p = 0.01). This difference was mainly due to a lower incidence of haemorrhagic stroke and did not result in a clear decline in mortality. In addition, these results are undermined by multiple methodological flaws. Clinical evaluation included no trials comparing apixaban with dabigatran; any indirect comparison would be risky given the poor quality of the clinical assessment of both drugs in atrial fibrillation. A double-blind, randomised trial including 5598 patients compared apixaban with aspirin but provided little information on these options in patients with a moderate risk of thrombosis, as most patients were at high risk. In clinical trials, major bleeding events were less frequent with apixaban than with warfarin (average 2.1 versus 3.1 events per 100 patient-years), but they were more frequent with apixaban than with aspirin (1.4 versus 0.9 events per 100 patient-years). In 2013, there is no way of monitoring the anticoagulant activity of apixaban in routine clinical practice, and there is no antidote in case of overdose; the same is true for dabigatran. Apixaban is a substrate for various cytochrome P450 isoenzymes and for P-glycoprotein, creating a risk of multiple drug-drug interactions. In addition, the anticoagulant action of apixaban is increased by renal failure, meaning that renal function must be regularly monitored. In practice, the antithrombotic treatment of choice for patients with atrial fibrillation is warfarin when the risk of thrombosis is high, and warfarin or aspirin when the thrombotic risk is moderate. When the INR cannot be maintained within the desired therapeutic range, it is best to stick with dabigatran.