Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus.

Authors:
Eri T Kato
Eri T Kato
Kyoto University Hospital
Kyoto | Japan
Michael G Silverman
Michael G Silverman
Brigham and Women's Hospital
Boston | United States
Ofri Mosenzon
Ofri Mosenzon
Hadassah University Hospital
Israel
Thomas A Zelniker
Thomas A Zelniker
Brigham and Women's Hospital and Harvard Medical School
Boston | United States
Avivit Cahn
Avivit Cahn
Hadassah Hebrew University Medical Center
Israel
Julia Kuder
Julia Kuder
Tufts University
United States
Sabina A Murphy
Sabina A Murphy
Brigham and Women's Hospital
Boston | United States

Circulation 2019 Mar 18. Epub 2019 Mar 18.

Medicine, BWH/TIMI Study Group, Boston, MA.

Background: In DECLARE-TIMI 58, the sodium glucose co-transporter 2 inhibitor (SGLT2i) dapagliflozin reduced the composite endpoint of cardiovascular (CV) death/ hospitalization for heart failure (HHF) in a broad population of patients with T2DM. However, the impact of baseline left ventricular ejection fraction (EF) on the clinical benefit of SGLT2i is unknown.

Methods: In the DECLARE-TIMI 58 trial, baseline HF status was collected from all patients and EF where available. HF with reduced EF (HFrEF) was defined as EF <45%. Outcomes of interest were the composite of CV death/HHF, its components, and all-cause mortality (ACM).

Results: Of 17,160 patients, 671 (3.9%) had HFrEF, 1316 (7.7%) had HF without known reduced EF and 15,173 (88.4%) had no history of HF at baseline. Dapagliflozin reduced CV death/HHF more in patients with HFrEF (HR 0.62, 95% CI 0.45-0.86) than in those without HFrEF (HR 0.88, 95% CI 0.76-1.02; P-interaction 0.046), in whom the treatment effect of dapagliflozin was similar in those with HF without known reduced EF (HR 0.88, 95% CI 0.66-1.17) and those without HF (HR 0.88, 95% CI 0.74-1.03). Whereas dapagliflozin reduced HHF both in those with (HR 0.64, 95%CI 0.43-0.95) and without HFrEF (HR 0.76, 95%CI 0.62-0.92), it reduced CV death only in patients with HFrEF (HR 0.55, 95% CI 0.34-0.90) but not in those without HFrEF (HR 1.08, 95% CI 0.89-1.31, P-interaction 0.012). Likewise, dapagliflozin reduced ACM in patients with HFrEF (HR 0.59, 95% CI 0.40-0.88), but not in those without HFrEF (HR 0.97, 95% CI 0.86-1.10, P-interaction 0.016).

Conclusions: In the first SGLT2i CV outcome trial to evaluate T2DM patients stratified by EF, we found that dapagliflozin reduced HHF in patients with and without HFrEF, and reduced CV death and ACM in patients with HFrEF.

Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT01730534.

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Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.119.040130DOI Listing
March 2019

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