While patients with atrial fibrillation (AF) and heart failure have increased mortality, they also have reduced rates of intracranial/any bleeding compared with patients without heart failure, according to a meta-analysis published in the Journal of the American College of Cardiology.
Novel oral anticoagulants (NOACS) are an ideal treatment option for patients with AF with concomitant heart failure because of the low bleeding risk associated with the use of these agents. However, there has not been sufficient research in this patient population to confirm whether NOACS are superior to warfarin in efficacy and safety.
Therefore, Gianluigi Savarese, MD, of Federico II University in Naples, Italy, and colleagues gathered data from the 4 major phase 3 NOAC clinical trials to determine if the efficacy or safety of NOACS differed among patients with AF and heart failure and those without heart failure. Stroke/systemic embolism; major, intracranial, and any bleeding; and cardiovascular and all-cause death served as the composite outcomes. Those trials included ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation), RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy), ROCKET-AF (Rivaroxaban Once Daily Oral Direct Factor Xa Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation), and ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation—Thrombolysis in Myocardial Infarction 48).
A total of 55,011 participants were included in the analysis: 24,384 with heart failure (13,351 treated with NOACS and 13,133 treated with warfarin) and 28,627 without heart failure (14,267 treated with NOACS and 14,360 treated with warfarin). Follow-up ranged from 1.5 to 2.8 years.
Stroke/systemic embolism rates were comparable between patients with and without heart failure. Specifically, the relative risk (RR) of stroke/systemic embolism was 0.98 (95% confidence interval [CI]:0.90-1.07; P =.68). With regard to major bleeding, the RR was 0.95 (95% CI: 0.88-1.03; P <.21). Patients with concomitant heart failure did have reduced rates of any/intracranial bleeding (any bleeding RR: 0.86; 95% CI: 0.81-0.91; P <.01 and intracranial bleeding RR: 0.74; 95% CI: 0.63-0.88; P <.01).
Nonetheless, regardless of heart failure status, use of NOACS significantly reduced stroke/systemic embolism and major, intracranial, and any bleeding rates (P interaction > .05 for each).
A limitation of this analysis is the different enrollment criteria for each trial, which is why some evidence points to higher thromboembolic risk in patients with AF with heart failure, but this is not seen consistently.
As Dr Savarese and colleagues pointed out, to be enrolled in any of the 4 trials, patients only had to have AF with one additional risk factor, including heart failure. Since other major risk factors for stroke/systemic embolism were necessary to fulfill the trial designs, there was a selection bias among patients without heart failure, which may have skewed the effect of heart failure on the risk of stroke/systemic embolism and bleeding. Moreover, the intention of these trials was not to assess NOACS in patients with or without heart failure specifically.
Savarese G, Giugliano RP, Rosano GMC, et al. Efficacy and safety of novel oral anticoagulants in patients with atrial fibrillation and heart failure: a meta-analysis. J Am Coll Cardiol. 2016. doi:10.1016/S0735-1097(15)60793-8.