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

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.

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.

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).

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.

CLINICAL TRIAL REGISTRATION:

URL: https://www.clinicaltrials.gov . Unique identifier: NCT01730534.

• Authors: Eri T Kato, Michael G Silverman, Ofri Mosenzon, Thomas A Zelniker, Avivit Cahn, Remo H M Furtado, Julia Kuder, Sabina A Murphy, Deepak L Bhatt, Lawrence A Leiter, Darren K McGuire, John P H Wilding, Marc P Bonaca, Christian T Ruff, Akshay S Desai, Shinya Goto, Peter A Johansson, Ingrid Gause-Nilsson, Per Johanson, Anna Maria Langkilde, Itamar Raz, Marc S Sabatine, Stephen D Wiviott
• Journal: Circulation (Circulation) Vol. 139 Issue 22 Pg. 2528-2536 (05 28 2019) ISSN: 1524-4539 [Electronic] United States
• PMID: 30882238 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Benzhydryl Compounds
• Cardiovascular Agents
• Glucosides
• Sodium-Glucose Transporter 2 Inhibitors
• dapagliflozin

Topics

• Aged
• Benzhydryl Compounds (adverse effects, therapeutic use)
• Cardiovascular Agents (adverse effects, therapeutic use)
• Cause of Death
• Diabetes Mellitus, Type 2 (diagnosis, drug therapy, mortality)
• Double-Blind Method
• Female
• Glucosides (adverse effects, therapeutic use)
• Heart Failure (diagnosis, drug therapy, mortality, physiopathology)
• Humans
• Male
• Middle Aged
• Risk Assessment
• Risk Factors
• Sodium-Glucose Transporter 2 Inhibitors (adverse effects, therapeutic use)
• Stroke Volume (drug effects)
• Time Factors
• Treatment Outcome
• Ventricular Function, Left (drug effects)