Registration: URL: Unique identifier: NCT01730534. This effect was consistent regardless of the patient's previous history of AF, atherosclerotic cardiovascular disease, or HF. Dapagliflozin also reduced the total number (first and recurrent) of AF/AFL events (337 versus 432 incidence rate ratio, 0.77 P=0.005).ĭapagliflozin decreased the incidence of reported episodes of AF/AFL adverse events in high-risk patients with type 2 diabetes mellitus. Moreover, there was no effect modification by sex, history of ischemic stroke, glycated hemoglobin A 1c, body mass index, blood pressure, or estimated glomerular filtration rate (all P for interaction >0.20). Similarly, presence of atherosclerotic cardiovascular disease (HR, 0.83 ) versus multiple risk factors (HR, 0.78 P for interaction 0.72) or a history of HF (HF: HR, 0.78 No HF: HR, 0.81 P for interaction 0.88) did not modify the reduction in AF/AFL events observed with dapagliflozin. The reduction in AF/AFL events was consistent regardless of presence or absence of a history of AF/AFL at baseline (previous AF/AFL: HR, 0.79 no AF/AFL: HR, 0.81 P for interaction 0.89). AF/AFL events were identified by search of the safety database using MedDRA preferred terms ('atrial fibrillation,' 'atrial flutter').ĭapagliflozin reduced the risk of AF/AFL events by 19% (264 versus 325 events 7.8 versus 9.6 events per 1000 patient-years hazard ratio, 0.81 P=0.009).

We explored the effect of dapagliflozin on the first and total number of AF/AFL events in patients with (n=1116) and without prevalent AF/AFL using Cox and negative binomial models, respectively. We therefore investigated whether SGLT2 inhibitors could also reduce the risk of AF/AFL.ĭECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58) studied the efficacy and safety of the SGLT2 inhibitor dapagliflozin versus placebo in 17 160 patients with type 2 diabetes mellitus and either multiple risk factors for atherosclerotic cardiovascular disease (n=10 186) or known atherosclerotic cardiovascular disease (n=6974). SGLT2 (sodium-glucose cotransporter 2) inhibitors have been shown to lower blood pressure, reduce weight, have salutary effects on left ventricular remodeling, and reduce hospitalization for HF and cardiovascular death in patients with type 2 diabetes mellitus. 12 AstraZeneca Gothenburg, Mölndal, Sweden (I.G.-N., A.M.L.).Ītrial fibrillation (AF) and atrial flutter (AFL) are associated with both diabetes mellitus and its related comorbidities, including hypertension, obesity, and heart failure (HF).11 Cardiología Clínica e Intervencionista Tarascos, Guadalajara, Mexico (F.P.).10 Department of Cardiology, Military Hospital, Budapest, Hungary (R.G.K.).9 Department of Cardiology, Centre of Postgraduate Medical Education, Grochowski Hospital, Warsaw, Poland (A.B.).8 Institute of Ageing and Chronic Disease, University of Liverpool, United Kingdom (J.P.H.W.).7 Division of Cardiology, University of Texas Southwestern Medical Center, Dallas (D.K.M.).Michael's Hospital, University of Toronto, Ontario, Canada (L.A.L.). 6 Li Ka Shing Knowledge Institute, St.5 The Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem, Israel (O.M., I.R.).4 Hospital Albert Einstein and Instituto do Coracao da Faculdade de Medicina da USP, Sao Paulo, Brazil (R.H.M.F.).

3 University of Colorado School of Medicine, Department of Medicine, Division of Cardiology, and CPC Clinical Research, Aurora (M.P.B.).

2 Division of Cardiology, Vienna General Hospital and Medical University of Vienna, Austria (T.A.Z.).

1 TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (T.A.Z., M.P.B., R.H.M.F., J.F.K., S.A.M., D.L.B., M.S.S., S.D.V.).

Declare timi 58