Physicians' Academy for Cardiovascular Education

DOAC treatment safe and effective in AF despite multi-morbidity

Outcomes of Apixaban versus warfarin in patients with atrial fibrillation and multi-morbidity: Insights from the ARISTOTLE trial

Literature - Alexander KP, Brouwer MA, Mulder H et al. - American Heart Journal 2018; S0002-8703(18)30296-5

Introduction and methods

Patients aged ≥70 years with atrial fibrillation (AF) often have multi-morbidity (≥3 comorbid conditions) [1], which is associated with polypharmacy, adverse events, and frailty potentially altering response to anticoagulation [2]. This post-hoc analysis of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial assessed the association between multi-morbidity and both efficacy and safety of apixaban compared with warfarin in older patients with AF.

The multicenter, double-blind ARISTOTLE trial compared apixaban with warfarin in 16,800 patients (aged ≥55 years old) with documented AF or atrial flutter with ≥1 risk factor for thromboembolism between 2006 and 2011, with a median follow-up of 1.8 years (IQR: 1.3-2.3). Eligible patients were randomized to receive apixaban 5 mg twice daily or dose-adjusted warfarin with a target INR of 2.0-3.0. A reduced dose of apixaban 2.5 mg twice daily was used for those patients with ≥2 of the following criteria at baseline: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL.

Patients were divided into groups based on the number of comorbidities: 0-2 (no multi-morbidity [36%]), 3-5 (moderate multi-morbidity [51%]) and ≥6 (high multi-morbidity [13%]). The primary efficacy outcome was stroke or systemic embolism (SE) and the primary safety outcome was major bleeding according to the International Society on Thrombosis and Hemostasis (ISTH) criteria [3].

Main results

Multi-morbidity and clinical outcomes

Multi-morbidity and effect of apixaban


In this post-hoc analysis of the ARISTOTLE trial, multi-morbidity was associated with an increased risk of stroke/SE, death, and major bleeding, however, efficacy and safety of apixaban compared with warfarin were preserved in older AF patients with multi-morbidity. These data support the use of apixaban for stroke prevention in AF among vulnerable patients with multi-morbidity. Further research is needed into the safety and efficacy of apixaban in the most complex AF patients.


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Find this article online at Am Heart J

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