3 research outputs found
Dapagliflozin and cardiovascular outcomes in type 2 diabetes
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.
Positionspapier Herzinsuffizienz und Diabetes.
Diabetes mellitus (DM) stellt eine wichtige Komorbidität bei Patienten
mit Herzinsuffizienz dar, die maßgeblich die Prognose der Patienten
determiniert. Von entscheidender Bedeutung zur Verbesserung der Prognose
dieser Hochrisiko-Patienten ist daher eine frühzeitige Diagnostik und
differenzierte medikamentöse Therapie mit Ausschöpfung aller möglichen
Therapieoptionen und Absetzen potenziell schädlicher Substanzen. Das
gemeinsame Positionspapier der Deutschen Gesellschaft für Kardiologie
(DGK) und der Deutschen Diabetes Gesellschaft (DDG) fasst die vorhandene
wissenschaftliche Evidenz zusammen und gibt Empfehlungen, was bei der
Diagnose und Therapie der Herzinsuffizienz und des DM zu beachten ist,
um die Prognose zu verbessern