Efficacy and Safety of Apixaban Compared With Aspirin in Patients Who Previously Tried but Failed Treatment With Vitamin K Antagonists: Results From the AVERROES Trial
What is the efficacy and safety of apixaban compared with aspirin in patients who previously tried but failed treatment with vitamin K antagonists (VKAs)?
The AVERROES double-blinded, randomized trial had reported that apixaban reduces the risk of stroke or systemic embolism (SSE) compared with aspirin without an increase in major bleeding in patients with atrial fibrillation either who previously tried but failed VKA therapy, or who were expected to be unsuitable for VKA therapy. In this prespecified analysis, the investigators explored the consistency of the results in the subgroup of patients who tried but failed VKA therapy. Of 5,599 patients, 2,216 (40%) had previously failed VKA treatment (main reasons: poor international normalized ratio [INR] control 42%, refusal 37%, bleeding on VKA 8%). The authors assessed the effect of apixaban versus aspirin on the risk or ischemic stroke or SSE and major bleeding in subgroups of patients who previously failed VKA therapy using Cox proportional-hazards regression models fitted separately within each level of a subgroup variable.
Compared with those expected to be unsuitable for VKA therapy, those who had previously failed were older, more often male, had higher body mass index, were more likely to have moderate renal impairment and a history of stroke, and less likely to have heart failure or to be medically undertreated. The effects of apixaban compared with aspirin were consistent in those who previously failed and those who were expected to be unsuitable, for both SSE (p interaction 0.13) and major bleeding (p interaction 0.74) and were also consistent among different subgroups of patients who had previously failed VKA therapy defined by reasons for unsuitability, age, sex, renal function, CHADS2 score, aspirin dose, duration, indication, and quality of INR control of prior VKA use.
The authors concluded that the efficacy and safety of apixaban compared with aspirin is consistent in subgroups of patients who have previously attempted but failed VKA therapy, irrespective of the reason for discontinuation.
This subgroup analysis indicates that the beneficial effects of apixaban versus aspirin found in the AVERROES trial apply across a wide spectrum of patients, irrespective of the reason for unsuitability of VKA therapy, including patients with prior bleeding episodes and patients with poor INR control. The optimal antithrombotic for patients who have failed treatment with VKAs remains a challenge. The results of the AVERROES trial show that aspirin monotherapy is inferior to twice-daily apixaban, and the newer anticoagulants may be an option in these patients. However, this subgroup analysis within the subgroup of patients who previously failed VKA therapy should be considered exploratory, and more robust prospective data are needed to define optimal antithrombotic therapy in patents who have failed treatment with VKAs.
Keywords: Vitamin K, Stroke, Body Mass Index, Heart Failure, Pyrazoles, Embolism, Pyridones, Hemorrhage
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