Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus - PubMed (original) (raw)
Randomized Controlled Trial
. 2019 May 28;139(22):2528-2536.
doi: 10.1161/CIRCULATIONAHA.119.040130. Epub 2019 Mar 18.
Michael G Silverman 2, Ofri Mosenzon 3, Thomas A Zelniker 4, Avivit Cahn 3, Remo H M Furtado 4, Julia Kuder 4, Sabina A Murphy 4, Deepak L Bhatt 4, Lawrence A Leiter 5, Darren K McGuire 6, John P H Wilding 7, Marc P Bonaca 8, Christian T Ruff 4, Akshay S Desai 9, Shinya Goto 10, Peter A Johansson 11, Ingrid Gause-Nilsson 11, Per Johanson 11, Anna Maria Langkilde 11, Itamar Raz 3, Marc S Sabatine 4, Stephen D Wiviott 4
Affiliations
- PMID: 30882238
- DOI: 10.1161/CIRCULATIONAHA.119.040130
Randomized Controlled Trial
Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus
Eri T Kato et al. Circulation. 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.
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.
Keywords: diabetes mellitus; heart failure; mortality; sodium-glucose transporter 2 inhibitors.
Comment in
- The Serendipitous Story of SGLT2 Inhibitors in Heart Failure.
Verma S, McMurray JJV. Verma S, et al. Circulation. 2019 May 28;139(22):2537-2541. doi: 10.1161/CIRCULATIONAHA.119.040514. Epub 2019 Mar 18. Circulation. 2019. PMID: 30882236 No abstract available. - Stratifying the effects of SGLT2i.
Fernández-Ruiz I. Fernández-Ruiz I. Nat Rev Cardiol. 2019 Jun;16(6):322. doi: 10.1038/s41569-019-0198-x. Nat Rev Cardiol. 2019. PMID: 30944408 No abstract available. - Letter by Elghazaly et al Regarding Article, "Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus".
Elghazaly H, Hajiev S, Singh P. Elghazaly H, et al. Circulation. 2019 Oct 29;140(18):e738-e739. doi: 10.1161/CIRCULATIONAHA.119.042627. Epub 2019 Oct 28. Circulation. 2019. PMID: 31657960 No abstract available.
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