Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial.

Alexander JH, Lopes RD, Thomas L et al.
Eur Heart J. 2013 Oct 20. [Epub ahead of print]

Background

Oral anticoagulants have been shown to be more effective for stroke prevention than antiplatelet therapy with aspirin alone (1,2] or aspirin plus clopidogrel [3] in patients with atrial fibrillation (AF). Patients with AF commonly also have coronary artery disease or other indications for aspirin [4,5].
High rates of bleeding have been observed with the combination of aspirin therapy and vitamin K antagonists (VKAs)[6-12]. Also in patients with recent acute coronary syndromes who were already on antiplatelet therapy, more bleedings were seen in patients receiving new oral anticoagulants as compared to placebo [13,14]. Based on these observations, it is recommended to combine antiplatelet and anticoagulant therapy for up to 12 months in patients with AF and a coronary stent and to then discontinue antiplatelet therapy [15-17].
The ARISTOTLE trial demonstrated superior efficacy of apixaban over warfarin in the prevention of stroke in patients with AF, and apixaban resulted in fewer major bleedings [18]. This analysis of the ARISTOTLE trial studied the efficacy and safety of apixaban compared with warfarin in patients receiving concomitant low-dose aspirin.

Main results

• Similar stroke reductions were seen with apixaban as compared to warfarin in aspirin users (1.12% vs. 1.91%, HR: 0.58, 95%CI: 0.39-0.85) and non-users (1.11% vs. 1.32%, HR: 0.84, 95%CI: 0.66-1.07, P for treatment interaction= 0.10). No effects of aspirin use on the effect of apixaban vs. warfarin on the rate of ischaemic stroke, myocardial infarction or death were seen.
• Apixaban resulted in consistent reductions in bleeding as compared to warfarin, in aspirin users (3.10% vs. 3.92% with warfarin, HR: 0.77, 95%CI: 0.60-0.99) and non-users (1.82% vs. 2.78%, HR: 0.65, 95%CI: 0.55-0.78, P for interaction: 0.29). Similarly, consistent benefits were seen with apixaban compared with warfarin among aspirin users and non-users for haemorrhagic stroke, major or clinically relevant non-major bleeding and any bleeding.
• Similar results were seen in analyses that accounted for whether a patient was taking aspirin at the time of bleeding.
• Correction for the propensity to use aspirin for differences in prognostically important baseline variables associated with aspirin use, aspirin users had similar outcome rates as compared to non-users. Only upon further correction for post-randomisation variables assoaciated with aspirin use, aspirin users tended to have higher rates of stroke or systemic embolism, ischaemic stroke and myocardial infarction.

Conclusion

This analysis of the ARISTOTLE trial demonstrates that the benefit of apixaban over warfarin in reduction stroke or systemic embolism in patients with AF is not affected by concomitant aspirin use. If there is a strong indication for simultaneous treatment with aspirin and oral anticoagulation, apixaban seems to be a safer option than warfarin.
Since in this study aspirin use was not blinded, nor randomised, further randomised clinical trials need to better define the optimal antithrombotic regimen and its duration in patients with both AF and an indication for antiplatelet therapy.

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