Something Else to Consider when Treating Atrial Fibrillation

January 31, 2017

Apixaban and warfarin have similar outcomes when used to treat atrial fibrillation patients with and without peripheral artery disease (PAD); although those with PAD had higher rates of death and stroke overall, according to a recent study.

Intraventricular clot lysis safe in severe stroke
Atrial Fibrillation: Updates and Insights

As rates of both PAD and AF increase, clinicians must continue to adapt to complex patient needs, balancing therapeutic efficacy and safety. Recent studies have shown that use of oral anticoagulation at baseline had no statistically significant impact on risk of stroke or systemic embolism in patients with PAD, but that bleeding risk did change based on the type of treatment.

In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, investigators led by Peter T Hu, Duke University Medical Center (Durham, NC), compared the safety and efficacy of apixaban and warfarin in patients with AF with and without PAD as well as the association of PAD in regards to stroke, systemic embolism, and bleeding.

The trial included 18,201 patients with AF and at least 1 risk factor for stroke. Patients were randomly assigned to twice-daily dosing of apixaban 5 mg or dose-adjusted warfarin. The primary efficacy outcome was ischemic or hemorrhagic stroke or systemic embolism. Investigators also examined how each treatment affected all-cause mortality. The primary safety outcome was major bleeding, with secondary outcomes of major bleeding and clinically relevant non-major bleeding.

PAD status was reported in 17,980 patients. Of those, 884 (4.9%) had PAD at baseline and were included in the final analysis. Overall, the unadjusted rates of stroke or systemic embolism were both higher among patients with PAD compared to without (HR 1.73, 95% CI 1.22–2.45; P=0.002), but after adjustment for differences in patient characteristics, no difference was present in rates of stroke or systemic embolism (HR 1.32, 95% CI 0.93–1.88; P=0.12). However, Patients with PAD had an increased risk of all-cause death (HR 1.36, 95% CI 1.11–1.67; P=0.003) and cardiovascular death (HR 1.44, 95% CI 1.08–1.90; P=0.01) versus those without PAD. Bleeding risk was similar for both patient groups.

The effect of apixaban versus warfarin for the prevention of stroke or systemic embolism was similar in patients with PAD (HR 0.63, 95% CI 0.32–1.25) and without PAD (HR 0.80, 95% CI 0.66–0.96; interaction P=0.52). Further, patients with PAD did not have any significant difference in ISTH major bleeding with apixaban compared with warfarin. The same was true of patients without PAD. This was also true of major or clinically relevant non-major bleeding risk.

From these results, the investigators concluded that while patients with AF and PAD had higher rates of death and stroke than patients without PAD, the benefits of apixaban compared with warfarin to control these symptoms were similar regardless of PAD status. These findings highlight the need to optimize the treatment of patients with AF and PAD.—Sean McGuire


Hu PT, Lopes RD, Stevens SR, et al. Efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation and peripheral artery disease: Insights from the ARISTOTLE trial. J Am Heart Assoc. 2017;6(1). doi: 10.1161/JAHA.116.004699.