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SGLT2 inhibitor reduces total HF events in patients with HFmrEF and HFpEF
Literature - Jhund PS, Claggett BL, Talebi A, et al. - JAMA Cardiol. 2023 Jun 1;8(6):554-563. doi: 10.1001/jamacardio.2023.0711


Trials with SGLT2 inhibitors have been designed to investigate the effects of SGLT2 inhibitors on time to first worsening HF event or CV death as primary outcome, and HF hospitalization as secondary outcome [1-4]. An investigation in the treatment effect of dapagliflozin on the total burden of HF, that is first and subsequent HF hospitalizations or urgent visits for HF and CV death in HFpEF and HFmrEF, is still lacking.

Aim of the study

The authors investigated the effects of dapagliflozin on total HF events in patients with HFmrEF and HFpEF.



This was a prespecified analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial. The DELIVER trial was a double-blind, event-driven, randomized clinical trial, in which 6263 patients with symptomatic HFmrEF/HFpEF (NYHA class II–IV HF symptoms, LVEF >40%, elevated NT-proBNP levels) were randomized to 10 mg dapagliflozin once daily or placebo. Patients were followed for a median period of 2.3 years. Two statistical methods were used to analyze total HF-events: the LWYY model and the joint frailty model.


The predefined outcome was total (first and repeated) worsening episodes of HF and CV death. In the DELIVER trial, the primary outcome was a composite of time to first worsening HF or CV death.

Main results

  • A lower rate of total HF events and CV death was detected in the dapagliflozin group compared with the placebo group (11.8 per 100 patient-years vs. 15.3 per 100 patient-years, respectively).
  • The LWYY rate ratio for total HF events was 0.77 (95%CI: 0.67-0.89; P<0.001). The HR of the primary composite endpoint of the DELIVER trial was 0.82 (95%CI: 0.73-0.92; P<0.001).
  • Using the joint frailty model, the rate ratio for HF events was 0.72 (95%CI: 0.65-0.81; P<0.001), and the rate ratio for CV death was 0.87 (95%CI: 0.72-1.05; P=0.14).
  • The effect of dapagliflozin on total HF events and CV death was consistent across any of the predefined DELIVER subgroups and across the spectrum of EF.


Dapagliflozin reduced the risk of total HF events (first and repeated events) compared with placebo in patients with HFmrEF and HFpEF. This benefit was consistent across different subgroups of patients, including across the spectrum of EF.


1. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008. doi:10.1056/NEJMoa1911303

2. Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022;387(12):1089-1098. doi:10.1056/NEJMoa2206286

3. Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020; 383(15):1413-1424. doi:10.1056/NEJMoa2022190

4. Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16): 1451-1461. doi:10.1056/NEJMoa2107038

Find this article online at JAMA Cardiol.

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Schedule24 May 2024