The SGLT2 inhibitors have been shown to prevent hospital admissions for HF in patients with type 2 diabetes and those with diagnosed heart disease or are at high risk and have been accorded Class 1 recommendation in these patients in the 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America (AHA/ACC/HFSA) guidelines for heart failure. They also make 2a recommendation for the class of SGLT2i for patients in HFmrEF.¹

The use of dapagliflozin reduced the total worsening heart failure (HF) events, both first and recurrent and cardiovascular (CV) death by 23% and this effect was consistent in patients with mildly reduced (HFmrEF) ejection fraction as well as those with preserved ejection fraction (HFpEF), according to a subgroup analysis of the DELIVER trial published online April 26, 2023 in JAMA Cardiology.2 More pertinently, this beneficial outcome of dapagliflozin was consistent in HFmrEF patients as well as HFpEF patients unlike the effect of empagliflozin on total hospitalizations for HF, which was seen to reduce in patient with higher ejection fraction in the in the EMPEROR-Reduced and EMPEROR-Preserved trials.

A team of researchers from the UK, United States, Sweden, Singapore, Argentina, The Netherlands carried out a prespecified analysis of the DELIVER trial published last year. A total of 6263 participants were enrolled for the present study from August 2018 to December 2020. More than half of the study population was male and the mean age of the study subjects was 71.7 years. The aim was to examine the effects of dapagliflozin 10 mg once daily (vs placebo) on total (first and recurrent) episodes of worsening HF. The proportional rates were calculated using the Lin, Wei, Yang, and Ying (LWYY) approach. The effect of dapagliflozin on total HF events and cardiovascular death was assessed using a joint frailty model.

Analysis showed fewer HF events and CV deaths in the dapagliflozin group compared to the placebo group; 815 vs 1057, respectively. Participants in whom HF events occurred more often had more severe HF manifesting as raised N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels, marked decline in kidney function, more hospital admissions previously for HF and longer duration of HF. However, the ejection fraction (EF) was similar between those with more HF events and patients with no HF events.

In the LWYY model, the rate ratio for total HF events and CV death was found to be 0.77 for dapagliflozin vs placebo. The hazard ratio in a traditional time to first event analysis was 0.82. In the joint frailty model, the rate ratio for total HF events with dapagliflozin was 0.72. For CV death, the rate ratio was 0.87.  All subgroups had similar results for total hospitalizations and cardiovascular death.

This study has shown the efficacy of dapagliflozin in reducing the predefined secondary end point, which was the risk of total HF events and CV deaths in HF patients. These events are preventable. “The reduction in burden of total HF events with dapagliflozin was evident regardless of the method used to analyze the total events and whether we examined total HF events including urgent HF visits or HF hospitalizations without urgent visits,” write the authors.

References

1. Heidenreich PA, et al. 2022 AHA/ACC/HFSA Guideline for the management of heart failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e895-e1032. Doi:10.1161/CIR.0000000000001063.
2. Jhund PS, 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. 2023 Apr 26. doi: 10.1001/jamacardio.2023.0711.