Risks of Heart Failure, Stroke, and Bleeding in Atrial Fibrillation According to Heart Failure Phenotypes.

BACKGROUND:The risks of heart failure (HF) events compared with stroke/systemic embolic events (SEE) or major bleeding (MB) in heart failure with reduced ejection fraction (HFrEF) vs heart failure with preserved ejection fraction (HFpEF) in a large atrial fibrillation (AF) population have not been well-studied. OBJECTIVES:This study sought to assess HF outcomes, according to HF history and HF phenotypes (HFrEF vs HFpEF), and compare these events with SEE and MB, among patients with AF. METHODS:We analyzed patients enrolled in the ENGAGE-AF TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in AF-Thrombolysis in Myocardial Infarction 48) trial. Cumulative incidence of heart failure hospitalization (HHF) or HF death was assessed and compared with the rates of fatal and nonfatal stroke/SEE and MB over a median follow-up of 2.8 years. RESULTS:Overall, 12,124 (57.4%) had a history of HF (37.7% HFrEF, 40.1% HFpEF, 22.1% with unknown ejection fraction). The rate per 100 person-years (py) of HHF or HF death (4.95; 95% CI: 4.70-5.20) was higher than of fatal and nonfatal stroke/SEE (1.77; 95% CI: 1.63-1.92) and MB (2.66; 95% CI: 2.47-2.86) among patients with HF history. HFrEF patients experienced a higher rate of HHF or HF death compared with HFpEF patients (7.15 vs 3.65; P < 0.001), while the rates of fatal and nonfatal stroke/SEE and MB were similar by HF phenotype. Patients with HF history had a higher rate of mortality after a HHF (1.29; 95% CI: 1.17-1.42) than after a stroke/SEE (0.69; 95% CI: 0.60-0.78) or after MB (0.61; 95% CI: 0.53-0.70). Overall, patients with nonparoxysmal AF had a higher rate of HF and stroke/SEE events regardless of HF history. CONCLUSIONS:Patients with AF and HF, regardless of ejection fraction, are at a higher risk of HF events with higher subsequent mortality rates than of stroke/SEE or MB. While HFrEF is associated with a higher risk of HF events than HFpEF, the risk of stroke/SEE and MB is similar between HFrEF and HFpEF.