Nonuse of oral anticoagulation and outcomes across the ejection-fraction spectrum in acute heart failure with atrial fibrillation
J Yamamoto, K Nakamura, Y Enomoto, H Hayama, M Yamamoto, H Hara, Y Hiroi, H HaraAbstract
Background
In acute heart failure (HF) with atrial fibrillation (AF), oral anticoagulation (OAC) is frequently withheld despite guideline recommendations, and it is uncertain whether the effectiveness and safety of OAC—including direct oral anticoagulants (DOACs)—are consistent across left-ventricular ejection fraction (LVEF) categories.
Purpose
To evaluate the effectiveness and safety of OAC strategies at discharge, and whether these associations differ across LVEF categories.
Methods
We analysed a multicentre cohort of 716 patients hospitalised for AF with HF (2014–2020). The primary exposure was use of any OAC at discharge (OAC vs no OAC). A secondary exposure compared DOACs with non-DOAC strategies (warfarin or no OAC). Among anticoagulated patients, we additionally compared DOAC versus warfarin. Outcomes were all-cause death, ischaemic stroke, and major bleeding. Cox models with stabilised inverse-probability weights (1st–99th percentile winsorised) were used. LVEF was assessed overall and within categories of <40%, 40–49%, and ≥50%. Sensitivity analyses used propensity-score trimming (0.05–0.95), overlap weighting, and doubly robust models. Effect modification by LVEF was assessed using a joint Wald test for treatment-by-LVEF interaction terms in weighted models.
Results
In the propensity-score analysis cohort (n=695), mean age was 79.1±11.3 years and 48.3% were women; 81.7% received OAC at discharge, and 63.6% of anticoagulated patients received a DOAC. LVEF was available in 678 patients (36% <40%, 18% 40–49%, 46% ≥50%). Over a median follow-up of 702 days, 185 deaths, 53 ischaemic strokes, and 86 major bleeds occurred. Compared with non-OAC, OAC use was associated with lower risks of all-cause death (HR 0.40, 95% CI 0.27–0.58; p < 0.001), ischaemic stroke (HR 0.23, 95% CI 0.12–0.44; p < 0.001), and major bleeding (HR 0.38, 95% CI 0.22–0.63; p = 0.001). DOAC use was associated with lower risks of all-cause death (HR 0.55, 95% CI 0.41–0.75; p < 0.001) and ischaemic stroke (HR 0.33, 95% CI 0.18–0.60; p = 0.002), while major bleeding did not differ significantly (HR 0.74, 95% CI 0.48–1.13; p = 0.229). Among anticoagulated patients, DOAC versus warfarin was associated with a lower risk of ischaemic stroke (HR 0.37 [0.17–0.79]; p = 0.010), without clear differences in all-cause death (HR 0.76 [0.51–1.12]; p = 0.159) or major bleeding (HR 1.00 [0.59–1.71]; p = 0.987). There was no significant interaction between OAC effects and LVEF categories for any outcome (all p for interaction > 0.25).
Conclusions
In AF with acute HF, OAC use at discharge was associated with substantially lower risks of death and ischaemic stroke without evidence of excess major bleeding, with benefits broadly consistent across the LVEF spectrum. DOAC-based strategies were at least as effective and safe as non-DOAC regimens, supporting guideline recommendations to preferentially use DOACs when OAC is indicated in this high-risk population.KM_OAC_unifiedPSFor image description, please refer to the figure legend and surrounding text.OAC as the referenceFor image description, please refer to the figure legend and surrounding text.