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CHICAGO -- Dapagliflozin (Farxiga) did not led to a difference in the rate of major adverse cardiovascular events (MACE) in diabetic patients with or at risk for atherosclerotic cardiovascular disease (ASCVD), but it did contribute to a lower rate of cardiovascular death or hospitalization for heart failure versus placebo, researchers reported here.

The composite of MACE (cardiovascular death, MI, or ischemic stroke) was 8.8% in the dapagliflozin group and 9.4% in the placebo group (hazard ratio 0.93, 95% CI 0.84-1.03, P=0.17 for superiority), according to Stephen Wiviott, MD, of Brigham and Women's Hospital in Boston, and colleagues.

The rate of cardiovascular death or hospitalization for heart failure was 4.9% for the dapagliflozin arm and 5.8% in the placebo arm (HR 0.83. 95% CI, 0.73-0.95, P=0.005 for superiority), they reported at the American Heart Association annual meeting and in the .

It is widely known that patients with type 2 diabetes are at an increased risk for adverse outcomes related to ASCVD, heart failure, and renal disease. The increased risk of heart failure among these patients is independent of coronary disease, the authors noted.

There is limited information in the existing literature to guide treatment for the prevention of heart failure, and considering the connection between diabetes, ASCVD, and heart failure, developing "diabetes therapies that are not only safe but also effective in reducing cardiovascular risk is paramount," they wrote.

Dapagliflozin is a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2) that promotes glucosuria in patients with type 2 diabetes, the authors explained.

The phase III DECLARE-TIMI 58 trial assessed "the effects of dapagliflozin on cardiovascular and renal outcomes in a broad population of patients who had or were at risk for atherosclerotic cardiovascular disease," the researchers stated.

AHA discussant Javed Butler, MD, MPH, MBA, of University of Mississippi in Jackson, called the trial "well conducted...and it stands out as having the highest proportion of patients with risk factor but without established ASCVD." It confirmed and replicated findings from prior research looking at SGLT2i [inhibitors] as it relates to safety, HbA1C, blood pressure, and weight.

However, SGLT2 inhibitor data cannot be taken in isolation from other type 2 diabetes trials and therapies, he cautioned.

DECLARE-TIMI 58 assessed 17,160 patients with type 2 diabetes over 4.2 years of follow-up. Of these, 6,974 had established CV disease and 10,186 had multiple risk factors. The patients had a mean age of 64 and 37% were female. Patients were randomly assigned to either the placebo arm or the dapagliflozin arm.

The authors reported that there were no differences between the two groups for cardiovascular death (HR 0.98, 95% CI 0.82-1.17).

Also, renal events occurred in 4.3% of the dapagliflozin group and in 5.6% of the placebo group (HR 0.76, 95% CI 0.67-0.87).

Death from any cause occurred in 6.2% of the dapagliflozin group and 6.6% in the placebo group (HR 0.93, 95% CI 0.82-1.04).

However, diabetic ketoacidosis was more common in the study drug group (0.3% vs 0.1% for placebo, P=0.02), as was the rate of genital infections (0.9% vs 0.1%. P<0.001), which led to regimen discontinuation or were considered serious adverse events.

Butler said that the concept of microvascular and macrovascular was vascular disease was arbitrary, and biologically overlapping rather than distinct concepts.

"Primary and secondary prevention cohort when defined for one disease or state may or may not be applicable to another disease or state," he stated. These trials and other data have shown that "for patients similar to those studied in the SGLT2i trials, these drugs should be used for [heart failure] risk reduction irrespective of their effect on MACE outcomes."

For other patient populations, such as those without risk factors or with those with heart failure, additional data are needed, Butler said.