Direct oral anticoagulants (DOACs) are at least as efficacious and safe as warfarin among non-valvular atrial fibrillation (NVAF) patients; limited evidence is available regarding NVAF patients with heart failure (HF). US Medicare enrollees with NVAF and HF initiating DOACs (apixaban, rivaroxaban, dabigatran) or warfarin were selected. Propensity score matching and Cox models were used to estimate the risk of stroke/systemic embolism (SE), major bleeding (MB), and major adverse cardiac events (MACE) comparing DOACs versus warfarin and DOACs versus DOACs. We identified 10,570 apixaban-warfarin, 4,297 dabigatran-warfarin, 15,712 rivaroxaban-warfarin, 4,263 apixaban-dabigatran, 10,477 apixaban-rivaroxaban, and 4,297 dabigatran-rivaroxaban matched pairs. Compared to warfarin, apixaban had lower rates of stroke/SE (hazard ratio = 0.64, 95% confidence interval = 0.48-0.85), MB (hazard ratio = 0.66, 0.58-0.76), and MACE (hazard ratio = 0.73,0.67-0.79); dabigatran and rivaroxaban had lower rates of MACE (hazard ratio = 0.87,0.77-0.99; hazard ratio = 0.84, 0.79-0.89, respectively). Rivaroxaban had a lower stroke/SE rate (hazard ratio = 0.65, 0.52-0.81) and higher MB rate (hazard ratio = 1.18, 1.08-1.30) versus warfarin. Compared to dabigatran and rivaroxaban, apixaban had lower MB (hazard ratio = 0.71, 0.57-0.89; hazard ratio = 0.55, 0.49-0.63) and MACE rates (hazard ratio = 0.80, 0.69-0.93; hazard ratio = 0.86, 0.79-0.94), respectively. All DOACs had lower MACE rates versus warfarin; differences were observed in stroke/SE and MB. Our findings provide insights about OAC therapy among NVAF patients with HF.

Current management practices for hyponatremia (HN) are incompletely understood. The HN Registry has recorded diagnostic measures, utilization, efficacy, and outcomes of therapy for eu- or hypervolemic HN. To better understand current practices, we analyzed data from 3087 adjudicated adult patients in the registry with serum sodium concentration of 130 mEq/l or less from 225 sites in the United States and European Union. Common initial monotherapy treatments were fluid restriction (35%), administration of isotonic (15%) or hypertonic saline (2%), and tolvaptan (5%); 17% received no active agent. Median (interquartile range) mEq/l serum sodium increases during the first day were as follows: no treatment, 1.0 (0.0-4.0); fluid restriction, 2.0 (0.0-4.0); isotonic saline, 3.0 (0.0-5.0); hypertonic saline, 5.0 (1.0-9.0); and tolvaptan, 4.0 (2.0-9.0). Adjusting for initial serum sodium concentration with logistic regression, the relative likelihoods for correction by 5 mEq/l or more (referent, fluid restriction) were 1.60 for hypertonic saline and 2.55 for tolvaptan. At discharge, serum sodium concentration was under 135 mEq/l in 78% of patients and 130 mEq/l or less in 49%. Overly rapid correction occurred in 7.9%. Thus, initial HN treatment often uses maneuvers of limited efficacy. Despite an association with poor outcomes and availability of effective therapy, most patients with HN are discharged from hospital still hyponatremic. Studies to assess short- and long-term benefits of correction of HN with effective therapies are needed.