Stroke and Systemic Embolism and Other Adverse Outcomes of Heart Failure With Preserved and Reduced Ejection Fraction in Patients With Atrial Fibrillation (from the COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation [CODE-AF]).

It is unknown whether heart failure (HF) with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) carry a similar risk of stroke or systemic embolism (SE) and other outcomes in patients with nonvalvular atrial fibrillation (AF). A prospective, multicenter outpatient registry with echocardiographic data which enrolled 10,589 patients from June 2016 to May 2019 was analyzed. In this registry, 935 (8.8%) patients had HF, and the proportions of patients with HFpEF and HFrEF were 43.2% and 56.8%, respectively. During follow-up over 1.33 years, 11 (2.07 per 100 person-years [PYR]) and 5 (0.76 per 100 PYR) patients had stroke/SE in the HFpEF and HFrEF groups, respectively, whereas 102 patients (0.84 per 100 PYR) had these sequelae in the no-HF group. The HFpEF group had a significantly higher cumulative incidence of stroke/SE (p = 0.004) and risk of stroke/SE (adjusted hazard ratio [HR] 2.23, 95% confidence interval [CI] 1.19 to 4.18) than the no-HF group. The risk of stroke/SE in the HFpEF group compared with that in the no-HF group was consistently increased even in patients on oral anticoagulation therapy (adjusted HR 2.55, 95% CI 1.31 to 4.96). There was a correlation between larger left atrial size and risk of stroke/SE (adjusted HR 1.53, 95% CI 1.03 to 2.29), but not between reduced left ventricular ejection fraction and this risk. In conclusion, these results suggest that strict oral anticoagulation therapy helps reduce the risk of stroke/SE in patients with nonvalvular AF and HFpEF, especially in those with a larger left atrial size.