Wiviott SD, et al. - Researchers investigated the impact of dapagliflozin, a selective inhibitor of sodium–glucose cotransporter 2, on cardiovascular outcomes in patients with type 2 diabetes. They did not observe any higher or lower rate of major adverse cardiovascular events (MACE) but a lower rate of cardiovascular death or hospitalization for heart failure with dapagliflozin treatment in type 2 diabetic patients who had or were at risk for atherosclerotic cardiovascular disease vs placebo—a finding that reflects a lower rate of hospitalization for heart failure.

Methods

• Type 2 diabetic patients who had or were at risk for atherosclerotic cardiovascular disease were randomized to receive either dapagliflozin or placebo.
• A composite of MACE—defined as cardiovascular death, myocardial infarction, or ischemic stroke—was assessed as primary safety outcome.
• Researchers evaluated MACE and a composite of cardiovascular death or hospitalization for heart failure as primary efficacy outcomes.
• A renal composite (≥ 40% decrease in estimated glomerular filtration rate to < 60 mL/minute/1.73 m² of body surface area, new end-stage renal disease, or death from renal or cardiovascular causes) and death from any cause were included secondary efficacy outcomes.

Results

• A total of 17,160 patients were assessed, including 10,186 without atherosclerotic cardiovascular disease, and followed for a median of 4.2 years.
• Findings revealed that the prespecified criterion for noninferiority to placebo with respect to MACE was met by dapagliflozin in the primary safety outcome analysis (upper boundary of the 95% CI, < 1.3; P < 0.001 for noninferiority).
• With dapagliflozin, no lower rate of MACE (8.8% in the dapagliflozin group and 9.4% in the placebo group) but a lower rate of cardiovascular death or hospitalization for heart failure (4.9% vs. 5.8%)—which reflected a lower rate of hospitalization for heart failure—was evident in the two primary efficacy analyses. There was no between-group difference in cardiovascular death.
• In the dapagliflozin group and in the placebo group, the occurrence of a renal event was reported in 4.3% and in 5.6%, respectively, and death from any cause in 6.2% and 6.6%, respectively.
• With dapagliflozin vs placebo, more common occurrence of diabetic ketoacidosis (0.3% vs 0.1%, P=0.02), as well as more common 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), were noted.