Ce-452776-1 early initiation of arni and sglt2i is associated with delayed atrial fibrillation in heart failure patients

Early use of mineralocorticoid receptor antagonists (MRA), sodium-glucose co-transporter inhibitors (SGLT2i) and angiotensin receptor-neprilysin inhibitors (ARNI) have shown benefit in major trials for heart failure patients and in other studies for recurrence of atrial fibrillation (AF) after ablation. Whether these medications and their resulting improved remodeling are associated with delayed onset of AF in a real-world heart failure cohort is unknown. We aimed to define the clinical phenotype of heart failure patients receiving early use (within 6 months) of MRA, SGLT2i, and ARNIs. We also investigated the association between use of these medications and time to first hospitalization with AF. We analyzed the electronic health records of the University of Pittsburgh Medical Center, a large multi-hospital system, between 2010 and 2022. Differences between baseline demographics, cardiovascular risk factors, and comorbidity burden were evaluated with t tests. Adjusted Cox proportional hazards models were performed to evaluate the association between early use of the medications and onset of AF for all heart failure patients and subgroups with reduced (HFrEF) and preserved (HFpEF) ejection fractions. Among 57689 patients, 2834 (5%) developed AF in the follow up period (median 3.3 years, IQR 4.7). A total 12015 (21%) had early initiation of MRA, 2259 (4%) SGLT2i, and 2909 (5%) ARNI. Patients receiving these medications were significantly more male with more commercial insurance, initial evaluation by cardiologists, and lower CHA2DS2VASC and Elixhauser comorbidity scores (table 1). In multivariate Cox models, delayed onset of AF hospitalization was associated with both use of early SGLT2i (HR 0.56, 95% CI 0.39-0.80, p<0.01) and ARNI (HR 0.52, 95% CI 0.39-0.70, p<0.001) but not MRA (figure 1). This trend was echoed in HFrEF patients (SGLT2i HR 0.46, 95% CI 0.24-0.89, p<0.05; ARNI HR 0.59, 95% CI 0.42-0.84, p<0.01) but associations were not significant in HFpEF. In a large, real-world cohort of heart failure patients, early use of ARNI and SGLT2i is significantly associated with delayed onset of AF. This association was driven largely by the HFrEF cohort. While only 5% of patients developed AF, early use of ARNI and SGLT2i in all indicated heart failure patients may decrease AF onset and morbidity in an already high-risk population.Tabled 1Table 1: Selected Baseline Characteristics of All Heart Failure Patients Receiving Early MRA, SGLT2i, and ARNI TherapyEarly Use of MRA-YESEarly Use of MRA-NOEarly Use of SGLT2i-YESEarly Use of SGLT2i-NOEarly Use of ARNI-YESEarly Use of ARNI-NOAge (mean±SD)67±14.172±13.865±12.671±14.065±13.571±14.0Male Sex (%)545061506550White Race (%)858987878488Commercial Insurance (%)242226222922Initial Evaluation by a Cardiologist (%)483947435540CHA2DS2VASC score (mean±SD)3.7±1.64.1±1.54.0±1.64.0±1.53.5±1.64.0±1.6Mean Elixhauser comorbidity score10.4119.210.91010.9Prior coronary revascularization (%)423346354735Confirmed HFrEF (%)301433165215Confirmed HFpEF (%)17231522423Early use of MRA (%)NANA48205619Early use of SGLT2i (%)93NANA273Early use of ARNI (%)14-NS3-NS35-NS4-NSNANANote: All pairs noted above are significant with p<0.01 except for those labeled "-NS", which are not significant. Open table in a new tab