The following is a summary of “Effect of Dapagliflozin on Cause-Specific Mortality in Patients With Heart Failure Across the Spectrum of Ejection Fraction” published in the October 2022 issue of Cardiology by Desai, et al.
Dapagliflozin has been proven to reduce the rate of the composite of worsening HF events or death from cardiovascular (CV) causes in 2 trials enrolling patients with heart failure (HF) throughout the spectrum of ejection fraction (EF). The purpose of this study was to investigate the impact of dapagliflozin on all-cause and cardiovascular mortality in EF. In addition, the purpose of this secondary analysis was to compare the effects of randomized treatment on cause-specific mortality between the DAPA-HF (participants with left ventricular ejection fraction [LVEF] ≤40%) and Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure or DELIVER trial (participant LVEF >40%) trials. Patients with chronic HF, New York Heart Association class II–IV, symptoms, 3and increased natriuretic peptides were randomly assigned to receive either dapagliflozin (10 mg, once daily) or placebo in the trials.
Each study’s primary outcome was a combined measure of CV mortality and HF worsening events (hospitalization or urgent heart failure visits). Clinical endpoints committees were blinded to therapy assignment and decided the causes of all clinical outcomes, including fatalities. Cox regression models were used to investigate the association between baseline EF and death mode and the impact of randomization on cause-specific mortality. In addition, the Poisson regression model was used to examine the associations with the continuous EF. About 1,628 deaths occurred among the 11,007 patients in the combined data set over the observation period (mean [SD] age, 71.7 [10.3] years; 1,139 male [70.0%]). It was revealed that cardiovascular disease was the cause of death for 872 (53.5%), other diseases for 487 (29.9%), and an unknown cause of death for 269 (16.5%). Out of the total number of deaths attributable to CV causes, 289 (33.1%) were caused by HF, 441 (50.6%) were unexpected, 69 (7.9%) were caused by stroke, 47 (5.4%) were caused by myocardial infarction, and 26 (3.1%) were caused by other CV causes.
Those with a higher EF had a higher death rate from causes other than CV. In the pooled population, treatment with dapagliflozin was linked to lower rates of CV death (hazard ratio [HR], 0.86; 95% CI, 0.75–0.98; P=.02). This was mostly due to lower rates of sudden death (HR, 0.84; 95% CI, 0.70–1.01; P =.07) and HF death (HR, 0.88; 95% CI, 0.70–1.11; P=.30), In a pooled analysis of patients with HF who took part in the DAPA-HF and DELIVER randomized clinical trials, dapagliflozin significantly lowered the risk of CV death across the whole range of LVEF. This was due to lower rates of sudden death and death from HF that got worse over time.