Similar Risk of Death Between Patients With HFimpEF, LVEF Above 40% in DELIVER Trial

In the DELIVER trial, patients with heart failure with improved ejection fraction (HFimpEF) had a similar risk of death compared with patients who had left ventricular ejection fraction (LVEF) consistently over 40%, according to a post hoc analysis of the DELIVER trial published in JAMA Cardiology.

The analysis also revealed an association between dapagliflozin use and reduced risk of cardiovascular death among individuals with HFimpEF—defined as prior LVEF of 40% or lower that has increased to over 40%—which seemed to be primarily driven by a lower residual risk of sudden death, according to the authors.

The DELIVER randomized clinical trial was conducted between August 2018 and December 2020. There, patients with HF with LVEF greater than 40%, New York Heart Association class II to IV symptoms, and elevated natriuretic peptides were randomly assigned to receive 10 mg daily of dapagliflozin or placebo. The current analysis focused on the mode of death concerning HFimpEF status and assessing the association between randomized treatment and cause-specific death using Cox regression models.

Man experiencing heart failure | Image credit: lovelyday12 – stock.adobe.com

Of 1151 patients with HFimpEF, 190 (16.5%) of them died. Meanwhile, of 5112 patients with LVEF consistently greater than 40%, 833 (16.3%) died.

Aside from having similar rates of death between the 2 patient groups, the distribution of mode of death was also similar. Among patients with HFimpEF and patients with high LVEF, 54% and 51% had a noncardiovascular death, while 46% and 49% had a cardiovascular death, respectively.

Sudden cardiac death was the most common type of cardiovascular death in both patient groups, accounting for 36 of 190 events (19%) in the HFimpEF group and 199 of 833 events (24%) in the LVEF above 40% group. HF-related death closely followed, making up 29 (15%) and 135 (16%) events in the HFimpEF and higher LVEF groups, respectively.

Among patients with HFimpEF specifically, the authors found lower rates of cardiovascular death among those who received dapagliflozin compared with placebo. According to the authors, this was primarily due to the lower rates of sudden death in the treatment group, with 10 events in the dapagliflozin arm and 26 in the placebo arm (HR, 0.38; 95% CI, 0.18-0.79; P for interaction = .01).

“The findings in this study support current guideline recommendations for use of sodium-glucose transport protein 2 inhibitor therapy, and further suggest that the addition of a sodium-glucose transport protein 2 inhibitor therapy to other guideline-directed medical therapies may help reduce cardiovascular mortality in patients with HFimpEF,” the authors concluded.

Limitations of this post hoc analysis include the small number of sudden death events, raising the possibility that the observed association between dapagliflozin and a lower risk of sudden death may be attributed to chance. Additionally, the classification of HFimpEF relied on a case report form question about prior LVEF 40% or lower, lacking information on the exact nadir of LVEF, time course, and magnitude of improvement. Consequently, alternative definitions of HFimpEF could not be explored, although sensitivity analysis using the European Society of Cardiology definition yielded similar findings, and the results were consistent irrespective of achieved LVEF.

Reference

Vardeny O, Desai AS, Jhund PS, et al. Dapagliflozin and mode of death in heart failure with improved ejection fraction: a post hoc analysis of the DELIVER trial. JAMA Cardiol. Published online January 24, 2024. doi:10.1001/jamacardio.2023.5318