Efficacy and Safety of Apixaban Compared With Warfarin According to Age for Stroke Prevention in Atrial Fibrillation: Observations From the ARISTOTLE Trial

Study Questions:

What is the efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation (AF)?


In this substudy of the ARISTOTLE trial, 18,201 patients with AF and a raised risk of stroke were randomized to warfarin or apixaban 5 mg bid, with dose reduction to 2.5 mg bid or placebo in 831 patients with ≥2 of the following criteria: age ≥80 years, body weight ≤60 kg, or creatinine ≥133 μmol/L. The authors used Cox models to compare outcomes in relation to patient age during 1.8 years of median follow-up.


Of the trial population, 30% were ages <65 years, 39% were 65 to <75 years, and 31% were ≥75 years. The rates of stroke, all-cause death, and major bleeding were higher in the older age groups (p < 0.001 for all). Apixaban was more effective than warfarin in preventing stroke and reducing mortality across all age groups, and associated with less major bleeding, less total bleeding, and less intracranial hemorrhage regardless of age (p interaction > 0.11 for all). Results were also consistent for the 13% of patients ages ≥80 years. No significant interaction with apixaban dose was found with respect to treatment effect on major outcomes.


The authors concluded that the benefits of apixaban versus warfarin were consistent in patients with AF regardless of age.


These observations from the ARISTOTLE substudy suggest that the risk of stroke, death, and major bleeding increases significantly with age, and that apixaban compared with warfarin reduces these outcomes in a consistent manner regardless of age, including in the group ages ≥80 years. As the absolute risks were higher in the older patient groups, the lack of interaction between treatment and age implies that the absolute benefits of apixaban were greater in the older population. Apixaban appears attractive for stroke prevention in AF across the spectrum of age, and particularly for the elderly. Future prospective trials are indicated to compare the efficacy and safety of newer anticoagulants with each other instead of aspirin or warfarin as a comparator.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Stroke, Intracranial Hemorrhages, Follow-Up Studies, Proportional Hazards Models, Warfarin, Atrial Fibrillation, Pyrazoles, Creatinine, Pyridones, Hemorrhage

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