Vascular and neurological outcomes in patients with atrial fibrillation treated with edoxaban; effects of cancer

Abstract

Abstract Introduction Data from novel oral anticoagulants (NOACs) trials has shown superior outcomes of NOACs compared to warfarin in vascular and bleeding events in patients with AF, both with and without cancer, however, little discussion has been provided on their effect in congestive heart failure (CHF). NOACs also may have biological benefits in Alzheimer disease (AD). We investigated the impact of edoxaban on vascular and bleeding events, CHF, and AD, in patients with AF, with and without cancer. Methods In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database, we identified a total of 5683 patients with non-valvular AF (NVAF) treated with edoxaban and matched them for gender and age to 11366 patients treated with warfarin. Subsequently, we similarly matched 703 patients with NVAF and cancer (NVAF-C) treated with edoxaban to 1406 patients treated with warfarin. The crude and adjusted hazard ratios (HRs) were applied for outcome assessments. Outcomes included arterial/venous ischemic events, CHF, Alzheimer disease (AD) , bleeding, acute kidney injury (AKI), and all-cause mortality.Results:Compared to warfarin, edoxaban showed significantly lower adjusted HRs for all-cause mortality (0.37 in NVAF, 0.39 in NVAF with cancer [NVAF-C]), hospitalization for gastrointestinal bleeding (0.74 in NVAF, 0.67 in NVAF-C), and CHF (0.26 in NVAF, 0.31 in NVAF-C) in both NVAF and NVAF-C groups (all p < 0.05). The adjusted HRs of acute myocardial infarction (0.71, p = 0.0051), peripheral artery disease (HR = 0.48, p < 0.001), venous thromboembolism (0.55, p = 0.0003), pulmonary embolism (0.20, p = 0.0002), and AD (0.66, p < 0.001) were also significantly lower for NVAF patients using edoxaban versus warfarin. However, edoxaban was associated with significantly higher adjusted HR of other hospitalized bleeding than warfarin (1.19, p = 0.0016) in NVAF patients but not in NVAF-C patients. Conclusion Edoxaban is associated with reduced risks of CHF in both NVAF and NVAF-C patients, and lower incidence of AD in NVAF when comparing to warfarin. These findings further support the use of edoxaban in patients with AF.