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Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus.
- Source :
-
Circulation [Circulation] 2019 May 28; Vol. 139 (22), pp. 2528-2536. Date of Electronic Publication: 2019 Mar 18. - Publication Year :
- 2019
-
Abstract
- Background: 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.<br />Methods: 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.<br />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 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).<br />Conclusions: 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.<br />Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01730534.
- Subjects :
- Aged
Benzhydryl Compounds adverse effects
Cardiovascular Agents adverse effects
Cause of Death
Diabetes Mellitus, Type 2 diagnosis
Diabetes Mellitus, Type 2 mortality
Double-Blind Method
Female
Glucosides adverse effects
Heart Failure diagnosis
Heart Failure mortality
Heart Failure physiopathology
Humans
Male
Middle Aged
Risk Assessment
Risk Factors
Sodium-Glucose Transporter 2 Inhibitors adverse effects
Time Factors
Treatment Outcome
Benzhydryl Compounds therapeutic use
Cardiovascular Agents therapeutic use
Diabetes Mellitus, Type 2 drug therapy
Glucosides therapeutic use
Heart Failure drug therapy
Sodium-Glucose Transporter 2 Inhibitors therapeutic use
Stroke Volume drug effects
Ventricular Function, Left drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4539
- Volume :
- 139
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Circulation
- Publication Type :
- Academic Journal
- Accession number :
- 30882238
- Full Text :
- https://doi.org/10.1161/CIRCULATIONAHA.119.040130