Physicians' Academy for Cardiovascular Education

Sustained benefit of SGLT2i in HFrEF by 28 days

Time to Clinical Benefit of Dapagliflozin and Significance of Prior Heart Failure Hospitalization in Patients With Heart Failure With Reduced Ejection Fraction

Literature - Berg DD, Jhund PS, Docherty KF, et al., - JAMA Cardiology 2021, doi:10.1001/jamacardio.2020.7585

Introduction and methods

The SGLT2 inhibitor dapagliflozin lowered risk of worsening heart failure events and CV death compared to placebo in HFrEF patients, demonstrated in the_DAPA-HF_trial (SGLT2 inhibitor reduces CV death and worsening HF events in HFrEF patients - PACE-CME ( [1]. Clinical inertia, which may be due to many therapeutic options for HFrEF patients nowadays, may lead to delayed initiation of therapy. This study examined the timing of onset of clinical benefit with dapagliflozin to estimate potential lost opportunities.

Hospitalization for worsening HF has substantial consequences for patient quality of life [2,3], and identifies patients at high risk for disease progression, CV death and those who require advanced therapies. In the DAPA-HF trial, almost half of the patients had been previously hospitalized [1]. This study examined whether risk of clinical events and effect of dapagliflozin varied as a function of proximity to the last HF hospitalization.

The DAPA-HF trial enrolled 4744 patients with HFrEF, who were randomized to dapagliflozin or placebo. Median follow-up was 18.2 months. Patients were excluded if they were currently hospitalized for acute decompensated HF or had been hospitalized for HF within 4 weeks of trial enrollment. For this analysis, patients were categorized according to timing of most recent HF hospitalization relative to trial enrollment: within the last 12 months, more than 12 months, or never. Primary efficacy outcome of the main trial was the composite of an episode of worsening HF or CV death.

Main results


Benefit of dapagliflozin in HFrEF patients in the DAPA-HF trial was rapidly apparent, with a sustained statistically significant benefit 28 days after randomization. Risk of primary outcome was higher in patients who were closer to a prior HF hospitalization, and relative (and absolute) risk reduction by dapagliflozin was higher in these patients.


Show references

Find this article online at JAMA Cardiol

Share this page with your colleagues and friends: