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

Kato, Eri T, Silverman, Michael G, Mosenzon, Ofri, Zelniker, Thomas A, Cahn, Avivit, Furtado, Remo HM, Kuder, Julia, Murphy, Sabina A, Bhatt, Deepak L, Leiter, Lawrence A
et al (show 13 more authors) (2019) Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus. CIRCULATION, 139 (22). pp. 2528-2536.

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<h4>Background</h4>In DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the composite end point of cardiovascular death/hospitalization for heart failure (HHF) in a broad population of patients with type 2 diabetes mellitus. However, the impact of baseline left ventricular ejection fraction (EF) on the clinical benefit of sodium-glucose cotransporter 2 inhibition is unknown.<h4>Methods</h4>In the DECLARE-TIMI 58 trial, baseline heart failure (HF) status was collected from all patients, and EF was collected when available. HF with reduced EF (HFrEF) was defined as EF <45%. Outcomes of interest were the composite of cardiovascular death/HHF, its components, and all-cause mortality.<h4>Results</h4>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 cardiovascular death/HHF more in patients with HFrEF (hazard ratio [HR], 0.62 [95% CI, 0.45-0.86]) than in those without HFrEF (HR, 0.88 [95% CI, 0.76-1.02]; P for 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 in those without HFrEF (HR, 0.76 [95% CI, 0.62-0.92]), it reduced cardiovascular 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 for interaction=0.012). Likewise, dapagliflozin reduced all-cause mortality 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 for interaction=0.016).<h4>Conclusions</h4>In the first sodium-glucose cotransporter 2 inhibitor cardiovascular outcome trial to evaluate patients with type 2 diabetes mellitus stratified by EF, we found that dapagliflozin reduced HHF in patients with and without HFrEF and reduced cardiovascular death and all-cause mortality in patients with HFrEF.<h4>Clinical trial registration</h4>URL: https://www.clinicaltrials.gov . Unique identifier: NCT01730534.

Item Type: Article
Uncontrolled Keywords: diabetes mellitus, sodium-glucose transporter 2 inhibitors, heart failure, mortality
Depositing User: Symplectic Admin
Date Deposited: 28 Mar 2019 14:25
Last Modified: 19 Jan 2023 00:55
DOI: 10.1161/CIRCULATIONAHA.119.040130
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3035221