Dapagliflozin Could Rapidly Curb Worsening Heart Failure, Death

In heart failure patients with reduced ejection fraction, dapagliflozin was associated with a rapid reduction in the risk of cardiovascular death or worsening heart failure, according to a secondary analysis of multinational trial data.

"In this secondary analysis of the DAPA-HF trial, we explored two key questions: how soon after starting dapagliflozin does this clinical benefit become apparent, and do patients who have been more recently hospitalized for heart failure experience a greater treatment benefit from dapagliflozin?" Dr. David Berg of Brigham and Women's Hospital in Boston told Reuters Health by email.

"The clinical benefit of dapagliflozin was rapidly apparent, with a significant benefit as soon as four weeks after starting therapy," he said. "Patients with a more recent heart failure hospitalization were at particularly high risk for bad outcomes and had a greater reduction in the risk of cardiovascular death and worsening heart failure."

Further, he said, "a particularly large benefit can be seen with prompt initiation in patients who have been hospitalized for heart failure in the past year."

​

The secondary analysis, published in JAMA Cardiology, included 4,744 patients with a mean age of 66.3 (23.4% women), including 2,251 (47.4%) who had previously been hospitalized for heart failure and 1,301 (27.4%) who had been hospitalized within 12 months prior to enrollment.

Patients were in New York Heart Association classes II through IV, with a left ventricular ejection fraction of 40% or less. The median follow-up time was 18.2 months.

The reduction in the primary outcome with dapagliflozin was rapid, with a sustained statistically significant benefit by day 28 (HR, 0.51).

There was a stepwise gradient of risk for the primary outcome among those receiving placebo according to timing of the most recent heart failure hospitalization. Two-year Kaplan-Meier rates were 21.1% for those never hospitalized for heart failure; 25.3%, for those hospitalized more than a year prior to the study; and 33.8% for those hospitalized within the last 12 months.

Across those subgroups, dapagliflozin reduced the relative risk of the primary outcome by 16% (HR, 0.84), 27% (HR, 0.73), and 36% (HR, 0.64), respectively.

The relative risk reductions, coupled with the higher baseline risk, led to correspondingly greater absolute risk reductions at two years across the groups: 2.1%, 4.1%, and 9.9%, respectively.

Dr. Berg noted, "The results of this analysis also set the stage for the ongoing DAPA ACT HF-TIMI 68, which is designed to evaluate the efficacy and safety of in-hospital initiation of dapagliflozin in patients with acute heart failure, a group that was excluded from DAPA-HF."

JAMA Cardiology Associate Editor Dr. Gregg Fonarow of the University of California, Los Angeles, coauthor of a related editorial, told Reuters Health, "These findings, along with complementary data from other trials, suggest that initiation of this medical therapy as soon as possible after a heart failure with reduced ejection fraction diagnosis, is a preferred strategy for improving patient-centered outcomes."

"Heart failure guidelines are in the process of being updated," he said by email. "The American College of Cardiology recently published a 2021 Update to Heart Failure management pathways that includes SGLT2 inhibitors as part of the standard of care for heart failure with reduced ejection fraction."

"However," he said, "despite the substantial clinical benefit and high value of these medications in treating patients with heart failure, there are barriers to (their) use, including restrictive formularies, prior authorization requirements, and significant out-of-pocket expenses faced by some patients."

"If these barriers can be overcome and optimal implementation of SGLT2 inhibitors for heart failure were achieved, over 34,000 lives a year in the US alone could be saved," Dr. Fonarow concluded.

The DAPA-HF trial was sponsored by AstraZeneca. Two coauthors are employees and many have received funds from the company. Dr. Fonarow has also received fees from the company.

—Marilynn Larkin

Source