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Circulation. 2019 Mar 18. doi: 10.1161/CIRCULATIONAHA.119.040130. [Epub ahead of print]

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

Author information

1
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan.
2
Medicine, Cardiology Division, Massachusetts General Hospital, Boston, MA.
3
Diabetes Unit Devision of Internal Medicine, Hadassah Hebrew University Hospital, Israel.
4
TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
5
Internal Medicine, Hadassah Hebrew University Hospital, Israel.
6
TIMI Study Group, Brigham and Women's Hospital, Boston, MA.
7
Statistics, TIMI Study Group, Brigham and Women's Hospital Heart & Vascular Center, Boston, MA.
8
TIMI Study Group, Brigham and Women's Hospital Heart & Vascular Center, Boston, MA.
9
Harvard Medical School, Brigham and Women's Hospital Heart and Vascular Center, Boston, MA.
10
Medicine, Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, Canada.
11
Internal Medicine-Cardiology, University of Texas-Southwestern Med Ctr, Dallas, TX.
12
Institute of Ageing and Chronic Disease, University of Liverpool, United Kingdom.
13
Colorado Prevention Center, CO.
14
Medicine, Brigham and Women's Hospital, Boston, MA.
15
Cardiolovascular Medicine, Brigham and Women's Hospital, Boston, MA.
16
Department of Medicine, Cardiology, Tokai University School of Medicine, Japan.
17
Biometrics, AstraZeneca, Sweden.
18
GMD, AstraZeneca Gothenburg, Sweden.
19
AstraZeneca R&D, CVRM, Sweden.
20
Biopharmaceuticals, AstraZeneca Gothenburg, Sweden.
21
Medicine, BWH/TIMI Study Group, Boston, MA.

Abstract

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.

KEYWORDS:

SGLT2 inhibitor

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