Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes

Cannon, C.P. and Pratley, R. and Dagogo‑Jack, S. and Mancuso, J. and Huyck, S. and Masiukiewicz, U. and Charbonnel, B. and Frederich, R. and Gallo, S. and Cosentino, F. and Shih, W.J. and Gantz, I. and Terra, S.G. and Cherney, D.Z.I. and McGuire, D.K. and Ukraine:, . and Godlevska, Olga and Chopey, Ivan and Teliatnikova, Zinaida and Kuskalo, Petro and Abrahamovych, Orest and Mankovskyi, Borys and Fushtey, Ivan and Myshanych, Galyna and Tykhonova, Susanna and Tseluyko, Vira and Koval, Olena and Parkhomenko, Oleksandr and Prokhorov, Oleksandr and Vayda, Myroslava and Martymianova, Larysa and Zharinova, Viktoriia and Prystupa, Lyudmyla and Pererva, Larysa and Kovalov, Oleksandr and Sokolova, Lyubov and Botsyurko, Volodymyr and Maslyanko, Vitaliy and Vlasenko, Maryna and Khomazyuk, Tetyana and Kulyk, Anna and Synenko, Volodymyr and Karpenko, Oleksandr and Mostovoy, Yuriy and Gyrina, Olga and Dolzhenko, Maryna and Donets, Oleksandra and Sorokina, Inna and Malynovsky, Yaroslav and Lysunets, Olena and Petrovskyy, Roman and Panina, Svitlana (2020) Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes. The New England Journal of Medicine = N Engl J Med, 383 (15). pp. 1425-1435. ISSN 0028-4793 (print); 1533-4406 (online)

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Abstract

BACKGROUND The cardiovascular effects of ertugliflozin, an inhibitor of sodium–glucose cotransporter 2, have not been established. METHODS In a multicenter, double-blind trial, we randomly assigned patients with type 2 diabetes and atherosclerotic cardiovascular disease to receive 5 mg or 15 mg of ertugliflozin or placebo once daily. With the data from the two ertugliflozin dose groups pooled for analysis, the primary objective was to show the noninferiority of ertugliflozin to placebo with respect to the primary outcome, major adverse cardiovascular events (a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke). The noninferiority margin was 1.3 (upper boundary of a 95.6% confidence interval for the hazard ratio [ertugliflozin vs. placebo] for major adverse cardiovascular events). The first key secondary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure. RESULTS A total of 8246 patients underwent randomization and were followed for a mean of 3.5 years. Among 8238 patients who received at least one dose of ertugliflozin or placebo, a major adverse cardiovascular event occurred in 653 of 5493 patients (11.9%) in the ertugliflozin group and in 327 of 2745 patients (11.9%) in the placebo group (hazard ratio, 0.97; 95.6% confidence interval [CI], 0.85 to 1.11; P<0.001 for noninferiority). Death from cardiovascular causes or hospitalization for heart failure occurred in 444 of 5499 patients (8.1%) in the ertugliflozin group and in 250 of 2747 patients (9.1%) in the placebo group (hazard ratio, 0.88; 95.8% CI, 0.75 to 1.03; P=0.11 for superiority). The hazard ratio for death from cardiovascular causes was 0.92 (95.8% CI, 0.77 to 1.11), and the hazard ratio for death from renal causes, renal replacement therapy, or doubling of the serum creatinine level was 0.81 (95.8% CI, 0.63 to 1.04). Amputations were performed in 54 patients (2.0%) who received the 5-mg dose of ertugliflozin and in 57 patients (2.1%) who received the 15-mg dose, as compared with 45 patients (1.6%) who received placebo. CONCLUSIONS Among patients with type 2 diabetes and atherosclerotic cardiovascular disease, ertugliflozin was noninferior to placebo with respect to major adverse cardiovascular events. (Funded by Merck Sharp & Dohme and Pfizer; VERTIS CV ClinicalTrials.gov number, NCT01986881.).

Item Type:	Article
Additional Information:	DOI: 10.1056/NEJMoa2004967 The authors’ full names, academic de‑ grees, and affiliations are listed in the Appendix. Address reprint requests to Dr. Cannon at Brigham and Women’s Hospi‑ tal, 360 Longwood Ave., 7th Fl., Boston, MA 02115, or at [email protected]. *A complete list of the VERTIS CV inves‑ tigators is provided in the Supplemen‑ tary Appendix, available at NEJM.org.
Subjects:	Internal Medicine
Divisions:	Departments > Department of Internal Medicine 2 and phthisiology Departments > Department of Internal Medicine 3 (formerly - hospital therapy 2) Departments > Department of Internal Medicine
Depositing User:	Елена Шрамко
Date Deposited:	02 Nov 2020 08:41
Last Modified:	02 Nov 2020 08:41
URI:	http://repo.dma.dp.ua/id/eprint/5905

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