Patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease had a lower rate of hospitalization for heart failure when treated with dapagliflozin compared with placebo, said researchers presenting findings from DECLARE-TIMI 58 on Nov. 10 during AHA 2018 in Chicago, IL. However, the findings, which were also published in the New England Journal of Medicine, did not show a difference in the overall rate of major adverse cardiovascular events (MACE) or cardiovascular death between the two groups.

Steven D. Wiviott, MD, FACC, and colleagues randomly assigned 17,160 patients, including 10,186 without atherosclerotic cardiovascular disease to dapagliflozin or placebo. The median follow-up was 4.2 years. The primary safety outcome was a composite of MACE and the primary efficacy outcomes were MACE and a composite of cardiovascular death or hospitalization for heart failure. Researchers also assessed renal composite and death from any cause.

Overall, dapagliflozin was noninferior to placebo with respect to the primary safety outcome and it did not result in a lower rate of MACE in terms of the primary efficacy outcome (8.8 percent in the dapagliflozin group vs. 9.4 percent in the placebo group). However, a lower overall composite rate of cardiovascular death or heart failure hospitalization was observed in the dapagliflozin group compared with placebo (4.9 percent vs. 5.8 percent), largely due to a difference in heart failure hospitalizations between the two groups.

"The lower rate of cardiovascular death or hospitalization for heart failure in the dapagliflozin group than in the placebo groups was consistent across multiple subgroups, which shows that dapagliflozin prevent cardiovascular events, particularly hospitalization for heart failure, in a broad range of patients, regardless of a history of atherosclerotic cardiovascular disease or heart failure," researchers said.

In other findings, a renal event occurred in 4.3 percent of patients in the dapagliflozin group compared with 5.6 percent in the placebo group. Death from any cause occurred in 6.2 percent of those assigned to dapagliflozin compared with 6.6 percent assigned to placebo. Researchers noted that these and other safety findings "add substantially to the literature on current safety concerns for this class of drugs [SGLT2i], which are based on relatively sparse previous data."

In related news, a separate review and meta-analysis of three separate trials, including DECLARE-TIMI 58, published Nov. 10 in The Lancet found SGLT2i to have moderate benefits on atherosclerotic MACE in patients with established atherosclerotic cardiovascular disease, but robust benefits on reducing hospitalization for heart failure and progression of renal disease regardless of existing atherosclerotic cardiovascular disease or a history of heart failure. The analysis also incorporated data from EMPA-REG OUTCOME and the CANVAS Program. "The present meta-analysis of SGLT2i cardiovascular outcome trials substantially expands on previous meta-analyses, and the totality of these data now makes several patterns clear," the authors said.

Keywords: AHA18, AHA Annual Scientific Sessions, Glucosides, Benzhydryl Compounds, Diabetes Mellitus

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