Dapagliflozin reduces first and recurrent HF hospitalization and CV death: DELIVER trial

The study, published in JAMA Cardiology, including 6263 patients, found that dapagliflozin reduced the risk of total heart failure (HF) events and cardiovascular death by 23%. This was consistent across a range of subgroups, including the EF spectrum.

Heart failure patients are hospitalized frequently for HF decompensation. With the increase in ejection fraction, the risk of death declines, but the hospitalization risk for HF remains relatively static across the EF spectrum. Therefore, repeated hospitalization contributes to a more significant proportion of the disease burden in patients with HF with preserved EF (HFpEF) or mildly reduced EF (HFmrEF) and is also associated with a greater subsequent risk of death.

Recently, it has been suggested that urgent visits for heart failure treatment can lead to worse outcomes. These events have been incorporated into time-to-first event composites along with HF hospitalizations.

"To our knowledge, the trials of SGLT2 inhibitors in HF still only examine the total number of HF hospitalization as a secondary outcome, and not the effect of treatment on the total burden of this condition indicated by the full spectrum of HF events from urgent visits through to cardiovascular death," the researchers wrote in their study.

In the prespecified analysis of the DELIVER trial, Pardeep S. Jhund, University of Glasgow, Glasgow, United Kingdom, and colleagues described in detail dapagliflozin's efficacy on total HF events, i.e. urgent visits for HF or first and recurrent HF hospitalizations and cardiovascular deaths, in the population with HFmrEF or HFpEF enrolled in the trial.

Several subgroups were examined to test for heterogeneity in the dapagliflozin's effect, including left ventricular EF. Participants' enrollment was done from 2018 to 2020, and data analysis was conducted from August to October 2022. Participants were randomized to 10 mg of dapagliflozin once daily or a matching placebo.

The study led to the following findings:

• Of 6263 included patients, 43.9% were women, and the mean age was 9.6 years.
• There were 1057 HF events and cardiovascular deaths in the placebo group compared with 815 in the dapagliflozin group.
• Patients with more HF events had features of more severe HF, such as higher N-terminal pro–B-type natriuretic peptide level, worse kidney function, more prior HF hospitalizations, and longer duration of HF. However, EF was similar to those with no HF events. In the LWYY model, the rate ratio for total HF events and cardiovascular death for dapagliflozin compared with placebo was 0.77, compared with a hazard ratio of 0.82 in traditional time-to-first event analysis.
• In the joint frailty model, the rate ratio was 0.72 for total HF events and 0.87 for cardiovascular death.
• The results were similar for total HF hospitalizations (without urgent HF visits) and cardiovascular death in all subgroups, including those defined by EF.

The researchers concluded, "HF events are common and preventable, and dapagliflozin's efficacy in reducing the number of these events is consistent across a broad range of subgroups and the EF spectrum."

Reference:

Jhund PS, Claggett BL, Talebi A, et al. Effect of Dapagliflozin on Total Heart Failure Events in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Prespecified Analysis of the DELIVER Trial. JAMA Cardiol. Published online April 26, 2023. doi:10.1001/jamacardio.2023.0711