Effect of Dapagliflozin on Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus: Insights From the DECLARE-TIMI 58 Trial
Abstract
Background: Atrial fibrillation (AF) and atrial flutter (AFL) are associated with both diabetes mellitus and its related comorbidities, including hypertension, obesity, and heart failure (HF). 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. We therefore investigated whether SGLT2 inhibitors could also reduce the risk of AF/AFL. Methods: DECLARE-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). 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. AF/AFL events were identified by search of the safety database using MedDRA preferred terms (“atrial fibrillation,” “atrial flutter”). Results: Dapagliflozin 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 [HR], 0.81 [95% CI, 0.68–0.95]; P =0.009). 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 [95% CI, 0.58–1.09]; no AF/AFL: HR, 0.81 [95% CI, 0.67–0.98]; P for interaction 0.89). Similarly, presence of atherosclerotic cardiovascular disease (HR, 0.83 [95% CI, 0.66–1.04]) versus multiple risk factors (HR, 0.78 [95% CI, 0.62–0.99]; P for interaction 0.72) or a history of HF (HF: HR, 0.78 [95% CI, 0.55–1.11]; No HF: HR, 0.81 [95% CI, 0.68–0.97]; P for interaction 0.88) did not modify the reduction in AF/AFL events observed with dapagliflozin. 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). Dapagliflozin also reduced the total number (first and recurrent) of AF/AFL events (337 versus 432; incidence rate ratio, 0.77 [95% CI, 0.64–0.92]; P =0.005). Conclusions: Dapagliflozin decreased the incidence of reported episodes of AF/AFL adverse events in high-risk patients with type 2 diabetes mellitus. This effect was consistent regardless of the patient’s previous history of AF, atherosclerotic cardiovascular disease, or HF. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01730534.
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Finerenone may reduce new-onset atrial fibrillation in patients with type 2 diabetes and chronic kidney disease.
“It has recently been reported that finerenone may reduce new-onset AF in patients with T2DM and CKD.605”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [605]
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- Authors
- Zelniker, T. A., Bonaca, M. P., Furtado, R. H. M., Mosenzon, O., Kuder, J. F., Murphy, S. A., Bhatt, D. L., Leiter, L. A., McGuire, D. K., Wilding, J. P. H., Budaj, A., Kiss, R. G., Padilla, F., Gause-Nilsson, I., Langkilde, A. M., Raz, I., Sabatine, M. S., & Wiviott, S. D.
- Affiliations
- Brigham and Women's Hospital (US)
- Hebrew University of Jerusalem (IL)
- St. Michael's Hospital (CA)
- The University of Texas Southwestern Medical Center (US)
- University of Liverpool (GB)
- Grochowski Hospital (PL)
- Department of Cardiology, Military Hospital, Budapest, Hungary (R.G.K.).
- Cardiología Clínica e Intervencionista Tarascos, Guadalajara, Mexico (F.P.).
- AstraZeneca Gothenburg, Mölndal, Sweden (I.G.-N., A.M.L.).
- AstraZeneca (Sweden) (SE)
- ORCID
- Venue
- Circulation
- Published
- 2020-04-14
- Volume
- 141
- Issue
- 15
- Pages
- 1227-1234
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W3004319546
- Cited by
- 459
- References
- 33
- Citations by year
- 2026: 49 · 2025: 79 · 2024: 87 · 2023: 67 · 2022: 72 · 2021: 72 · 2020: 33
- FWCI
- 45.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AstraZeneca
- Brigham and Women's Hospital
- Harvard University
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- dapagliflozin, atrial fibrillation, atrial flutter, type 2 diabetes, SGLT2 inhibitors, DECLARE-TIMI 58, atherosclerotic cardiovascular disease, cardiovascular risk reduction, heart failure, hypertension, obesity, left ventricular remodeling, anticoagulation, atrial fibrillation risk stratification, atrial fibrillation recurrence
- MeSH terms
- Atrial Fibrillation, Benzhydryl Compounds, Diabetes Mellitus, Type 2, Female, Glucosides, Humans, Male
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