Dapagliflozin and cardiovascular outcomes in type 2 diabetes

Wiviott, S.D. and Raz, I. and Bonaca, M.P. and Mosenzon, O. and Kato, E.T. and Cahn, A. and Silverman, M.G. and Zelniker, T.A. and Kuder, J.F. and Murphy, S.A. and Bhatt, D.L. and Leiter, L.A. and McGuire, D.K. and Wilding, J.P.H. and Ruff, C.T. and Gause‑Nilsson, I.A.M. and Fredriksson, M. and Johansson, P.A. and Langkilde, A.-M. and Sabatine, M.S. and for the DECLARE–TIMI 58 Investigators* and Ukraine: and Karpenko, O. and Tkach, S. and Vlasenko, M. and Fushtey, I. and Pertseva, T. and Reshotko, D. and Mostovoy, Y. and Vizir, V. and Kraiz, I. and Amosova, K. and Batushkin, V. and Tseluyko, V. and Koval, O. (2019) Dapagliflozin and cardiovascular outcomes in type 2 diabetes. The New England Journal of Medicine = N Engl J Med, 380 (4). pp. 347-357. ISSN 0028-4793 (print); 1533-4406 (online)

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Abstract

BACKGROUND The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium– glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined. METHODS We randomly assigned patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease to receive either dapagliflozin or placebo. The primary safety outcome was a composite of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or ischemic stroke. The primary efficacy outcomes were MACE and a composite of cardiovascular death or hospitalization for heart failure. Secondary efficacy outcomes were a renal composite (≥40% decrease in estimated glomerular filtration rate to <60 ml per minute per 1.73 m2 of body-surface area, new end-stage renal disease, or death from renal or cardiovascular causes) and death from any cause. RESULTS We evaluated 17,160 patients, including 10,186 without atherosclerotic cardiovascular disease, who were followed for a median of 4.2 years. In the primary safety outcome analysis, dapagliflozin met the prespecified criterion for noninferiority to placebo with respect to MACE (upper boundary of the 95% confidence interval [CI], <1.3; P<0.001 for noninferiority). In the two primary efficacy analyses, dapagliflozin did not result in a lower rate of MACE (8.8% in the dapagliflozin group and 9.4% in the placebo group; hazard ratio, 0.93; 95% CI, 0.84 to 1.03; P=0.17) but did result in a lower rate of cardiovascular death or hospitalization for heart failure (4.9% vs. 5.8%; hazard ratio, 0.83; 95% CI, 0.73 to 0.95; P=0.005), which reflected a lower rate of hospitalization for heart failure (hazard ratio, 0.73; 95% CI, 0.61 to 0.88); there was no between-group difference in cardiovascular death (hazard ratio, 0.98; 95% CI, 0.82 to 1.17). A renal event occurred in 4.3% in the dapagliflozin group and in 5.6% in the placebo group (hazard ratio, 0.76; 95% CI, 0.67 to 0.87), and death from any cause occurred in 6.2% and 6.6%, respectively (hazard ratio, 0.93; 95% CI, 0.82 to 1.04). Diabetic ketoacidosis was more common with dapagliflozin than with placebo (0.3% vs. 0.1%, P=0.02), as was the rate of genital infections that led to discontinuation of the regimen or that were considered to be serious adverse events (0.9% vs. 0.1%, P<0.001). CONCLUSIONS In patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease, treatment with dapagliflozin did not result in a higher or lower rate of MACE than placebo but did result in a lower rate of cardiovascular death or hospitalization for heart failure, a finding that reflects a lower rate of hospitalization for heart failure. (Funded by AstraZeneca; DECLARE–TIMI 58 ClinicalTrials.gov number, NCT01730534.)

Item Type:	Article
Additional Information:	The authors’ full names, academic degrees, and affiliations are listed in the Appendix. Ukraine: O. Karpenko, City Clinical Hospital #1, Department of Emergency Cardiology, Kyiv; S. Tkach, SI IEM n.a. V.P.Komisarenko of AMS of Ukraine Diabetology Dept, Kyiv; M. Vlasenko, Vinnytsa Reg.Clin.Endocrin.Disp.,VSMU n.a. M.I.Pirogov, Endocrin dept., Vinnytsia; I. Fushtey, Zaporizhzhya Centr Hosp of Voznesenovsky district. Zaporizhzhya MAPE, Zaporizhzhya; T. Pertseva, lSSClinica of medical academy of SEDnepropetrovsk Med.Acad. of MOH, Dnipro; D. Reshotko, Kyiv Oleksandrivska Clinical Hospital, Dept of Myocard. Infarction #1, Kyiv; Y. Mostovoy, Private Small-Scale Enterprise, Medical Center Pulse, Vinnytsia; V. Vizir, MI Zaporizhzhya City Hospital #7, Dept of Cardiology, Zaporizhzhya; I. Kraiz, Kharkiv Centr. Clin. Hospital of Ukrzaliznitsia, Cardiological Dept, Kharkiv; K. Amosova, Kyiv Oleksandrivska Clinical Hospital, Dept of rehabilitation, Kyiv; V. Batushkin, Kyiv Municipal Clin. Hosp. #5, Myocard. Infarct. and Intens. Care Unit, Kyiv; V. Tseluyko, Kharkiv Municipal Clin. Hosp. #8, Dept of Cardiology and Funct. Diagn., Kharkiv; O. Koval, Dnipro Municipal Joint Emergency Hospital, Cardiology Dept PMI, Dnipro
Subjects:	Diabetes Clinical medicine
Divisions:	Departments > Department of Internal Medicine 1 (formerly - Faculty Therapy and Endocrinology) Departments > Department of Internal Medicine 3 (formerly - hospital therapy 2)
Depositing User:	Елена Шрамко
Date Deposited:	21 May 2021 13:03
Last Modified:	24 May 2021 07:56
URI:	http://repo.dma.dp.ua/id/eprint/6550

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