Physicians' Academy for Cardiovascular Education

Early and sustained clinical benefits with SGLT2i in HFmrEF/HFpEF

Time to Clinical Benefit of Dapagliflozin in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Prespecified Secondary Analysis of the DELIVER Randomized Clinical Trial

Literature - Vaduganathan M, Claggett BL, Jhund P, et al. - JAMA Cardiol. 2022 Dec 1;7(12):1259-1263. doi: 10.1001/jamacardio.2022.3750

Introduction and methods


Recently, the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial showed that dapagliflozin reduced the incidence of CV death or worsening HF events compared with placebo in patients with HFmrEF or HFpEF [1]. While prevention of worsening HF is a priority in the comprehensive management of this patient population [2], it is uncertain when worsening HF events may occur. Knowledge of the expected time course to disease stabilization or even clinical improvement may be of interest to both patients and their treating physicians.

Aim of the study

In a prespecified secondary analysis of the DELIVER trial, the authors aimed to evaluate the time course of benefits of dapagliflozin treatment on clinically relevant outcomes in patients with HFmrEF or HFpEF.


The DELIVER trial was a global, event-driven, phase 3 RCT in which 6263 patients with symptomatic HFmrEF or HFpEF (LVEF >40%) were randomized to dapagliflozin 10 mg once daily or matching placebo between August 2018 and December 2020. The timeline to onset of clinical benefit with dapagliflozin versus placebo was assessed, whereby data were truncated at every day postrandomization.


The primary endpoint was a composite outcome of time to first occurrence of CV death or worsening HF (i.e., hospitalization for HF or urgent HF visit requiring intravenous HF therapies).

Main results


In this prespecified analysis of the DELIVER trial, dapagliflozin treatment led to early and sustained reductions in the incidence of CV death or worsening HF in patients with HFmrEF or HFpEF compared with placebo. Within 2 weeks of treatment initiation, a statistically significant reduction in the primary endpoint was seen. The authors acknowledge that “[f]or less frequent events in HFmrEF/HFpEF, such as CV death or kidney disease progression, the anticipated timeline to clinical benefit and duration necessary to demonstrate statistical significance may be longer.”


Show references

Find this article online at JAMA Cardiol.

Share this page with your colleagues and friends: