|The following article is part of conference coverage from the 2018 AHA Scientific Sessions in Chicago, Illinois.The Cardiology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in cardiology. Check back for the latest news from AHA 2018.|
CHICAGO — Once-daily dapagliflozin at a single 10-mg dose was not associated with either a higher or lower rate of major adverse cardiovascular events (MACE) compared with placebo in patients with type 2 diabetes (T2D) who had or were at risk for atherosclerotic cardiovascular disease, according to research presented at the American Heart Association Scientific Sessions 2018 held November 10-12, 2018, in Chicago, Illinois,1 and simultaneously published in the New England Journal of Medicine.2
Despite these findings, dapagliflozin 10 mg once per day was associated with lower rates of cardiovascular death or hospitalization for heart failure (HF) in this study, the researchers reported.
Patients with T2D age ≥40, a glycated hemoglobin level of ≥6.5%, and multiple risk factors for or established atherosclerotic cardiovascular disease were enrolled in randomized, double-blind, multinational, placebo-controlled phase 3 trial (DECLARE-TIMI 58, ClinicalTrials.gov Identifier: NCT01730534). Investigators randomly assigned eligible patients to receive either 10 mg dapagliflozin once per day (n=8582) or placebo (n=8578).
The incidence of MACE and a composite of cardiovascular death or HF-related hospitalization comprised the primary efficacy outcomes. Additional efficacy outcomes included death from any cause, as well as a renal composite comprised of new end-stage renal disease, ≥40% decrease in estimated glomerular filtration rate to <60 ml per minute per 1.73 m2 of body-surface area, renal- or cardiovascular-related death, and death from any cause.
During median 4.2-year follow-up, treatment with once-daily dapagliflozin did not confer a significantly greater benefit to patients compared with placebo with regard to the primary efficacy outcomes (upper boundary of the 95% CI, <1.3; P <.001 for noninferiority).
Dapagliflozin was not associated with a lower MACE rate compared with placebo (8.8% vs 9.4%, respectively; hazard ratio [HR], 0.93; 95% CI, 0.84-1.03; P =.17).
Treatment with dapagliflozin did result in significantly lower rates of cardiovascular death or HF hospitalization compared with placebo (4.9% vs. 5.8%, respectively; HR, 0.83; 95% CI, 0.73-0.95; P =.005).
No between-group difference was observed in the incidence of cardiovascular death during the study period (HR, 0.98; 95% CI, 0.82-1.17). A lower percentage of patients in the dapagliflozin group experienced a renal event (4.3% vs 5.6%; HR, 0.76; 95% CI, 0.67-0.87), whereas a similar percentage of patients in the dapagliflozin and placebo groups experienced death from any cause (6.2% and 6.6%, respectively; HR, 0.93; 95% CI, 0.82-1.04).
Dapagliflozin was associated with a greater rate of diabetic ketoacidosis (0.3% vs 0.1%; P =.02), as well as genital infections that resulted in regimen discontinuation (0.9% vs 0.1%; P <.001).
While no superior benefit was found for dapagliflozin vs placebo with regard to MACE, the study data “suggest that in patients without established atherosclerotic cardiovascular disease, sodium–glucose cotransporter 2 inhibition [with dapagliflozin] can prevent serious clinical events, particularly hospitalization for heart failure, and possibly reduce the likelihood of progression of renal disease,” the study investigators noted.
Disclosures: DECLARE-TIMI 58 was funded by AstraZeneca. Please refer to original reference for full list of disclosures.
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- Wiviott SD, Raz I, Bonaca MP, et al. The Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial. Presented at: American Heart Association Scientific Sessions 2018; November 10-12, 2018; Chicago, Illinois. Session LBS.02 – Late Breaking Clinical Trial: Novel Approaches to CV Prevention
- Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes [published online November 10, 2018]. NEJM. doi:10.1056/NEJMoa1812389