HEART FAILURE OUTCOMES IN PATIENTS WITH DIABETES WITH AND WITHOUT ATRIAL FIBRILLATION - DATA FROM THE EMPA-REG OUTCOME STUDY

Abstract

Atrial fibrillation (AF) is a frequent comorbidity in heart failure (HF) that worsens outcomes, reflecting more advanced myocardial disease. AF confers an additional risk associated with HF, and HF treatments, such as beta blockers, have not reduced mortality in patients with AF. In the EMPA-REG OUTCOME study, empagliflozin (EMPA) reduced HF hospitalizations (HHF), cardiovascular (CV) death, HHF/CV death, and incident/worsening nephropathy in patients with type 2 diabetes (T2D) and established CV disease. This post-hoc analysis of EMPA-REG OUTCOME examined (1) classical and expanded HF outcomes in a T2D population with and without pre-existing AF, and (2) the effect of EMPA in patients with and without AF. In total, 7020 patients with T2D and CV disease were treated with EMPA 10 mg, 25 mg or placebo (PBO), with a median follow up of 3.1 years. We explored the association between investigator-reported history of AF at baseline and time to first HHF, CV death, HHF/CV death, introduction of loop diuretics, occurrence of edema and incident/worsening nephropathy. We also assessed the consistency of the effect of EMPA in patients with and without AF at baseline. Differences in risks between groups were assessed using a Cox proportional hazards model with factors for age, sex, baseline body mass index (BMI), baseline glycated hemoglobin, baseline estimated glomerular filtration rate (eGFR), region, treatment, AF and treatment by AF interaction. All analyses were performed on a nominal two-sided alpha of 0.05 without adjustment for multiplicity. Overall, 389 patients had investigator-reported AF at baseline. Patients with AF were more often male (78.1 vs 71.1%), older (mean age 68.4 vs 62.8 years), had higher BMI (mean 31.7 vs 30.6 kg/m2), and lower eGFR (mean 67.4 vs 74.4 ml/min/1.73 m2). Furthermore, in PBO and EMPA-treated patients, rates of HHF/CV death were higher in patients with vs without AF at baseline (PBO/EMPA 23.2/15.4% vs 7.5/5.1%). Increased risks were also detected for HHF (PBO/EMPA 12.7/8.5% vs 3.5/2.4%), introduction of loop diuretics (PBO/EMPA 25.6/18.5% vs 12.7/8.2%), first occurrence of edema (PBO/EMPA 16.2/5.7% vs 9.7/5.3%) and incident/worsening nephropathy (PBO/EMPA 24.6/12.6% vs 18.5/12.7%). EMPA consistently reduced HHF, CV death, HHF/CV death, introduction of loop diuretics, occurrence of edema and incident/worsening nephropathy in patients with and without AF (Figure). In patients with T2D and CV disease, AF is associated with an increased risk of CV and HF outcomes and mortality. The treatment effects of EMPA are consistent in patients with and without AF.