Wiviott, SD, Raz, I, Bonaca, MP, Mosenzon, O, Kato, ET, Cahn, A, Silverman, MG, Zelniker, TA, Kuder, JF, Murphy, SA et al (show 10 more authors)
(2019)
Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes.
NEW ENGLAND JOURNAL OF MEDICINE, 380 (4).
pp. 347-357.
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Abstract
<h4>Background</h4>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.<h4>Methods</h4>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 m<sup>2</sup> of body-surface area, new end-stage renal disease, or death from renal or cardiovascular causes) and death from any cause.<h4>Results</h4>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).<h4>Conclusions</h4>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 |
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Uncontrolled Keywords: | DECLARE–TIMI 58 Investigators, Humans, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Benzhydryl Compounds, Glucosides, Hospitalization, Aged, Middle Aged, Female, Male, Heart Failure, Sodium-Glucose Transporter 2 Inhibitors |
Depositing User: | Symplectic Admin |
Date Deposited: | 22 Nov 2018 10:36 |
Last Modified: | 19 Jan 2023 01:12 |
DOI: | 10.1056/NEJMoa1812389 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3029005 |