Dapagliflozin Improves Heart Failure-Related Health Status in HFrEF

heart failure, dilated cardiomyopathy
Dapagliflozin use was linked to an in increase in the proportion of patients experiencing clinically meaningful improvements in HF-related health status in HFrEF.

Although dapagliflozin did not affect mean N-terminal pro b-type natriuretic peptide (NT-proBNP) levels in persons with heart failure with reduced ejection fraction (HFrEF), the proportion of patients demonstrating clinical improvements heart failure-associated health status increased, according to study results published in Circulation.

Researchers assessed results from the DEFINE-HF trial, a randomized, placebo-controlled, double-blind trial of 263 individuals with HFrEF. Heart failure with reduced ejection fraction was defined as New York Heart Association class II or III, ≥16 weeks of diagnosed HF, left ventricular ejection fraction ≤40%, estimated glomerular filtration rate ≥30 mL/min/1.73 m², and high natriuretic peptides. Researchers randomly assigned participants to standard care plus daily dapagliflozin 10 mg (n=131) or placebo (n=132) for 12 weeks.

Using the Kansas City Cardiomyopathy Questionnaire (KCCQ), researchers defined the primary objectives as (1) average 6- and 12-week adjusted mean NT-proBNP and (2) proportions of individuals with improved HF-related health status (threshold, ≥5-point KCCQ increase) or NT-proBNP (threshold, ≥20% decrease). They used a generalized linear mixed model to evaluate mean NT-proBNP, and they used logistic regression to evaluate the proportional HF-related improvements for dapagliflozin vs placebo.

Adjusted mean NT-proBNP did not vary significantly between dapagliflozin (1133 pg/dL; 95% CI, 1036-1238) and placebo (1191 pg/dL; 95% CI, 1089-1304 pg/dL; P =.43); however, more patients treated with dapagliflozin showed clinical improvement in HF-related health status or decreased NT-proBNP compared with placebo (61.5% vs 50.4%; adjusted odds ratio [AOR], 1.8; 95% CI, 1.03-3.06; P =.039).

Specifically, dapagliflozin vs placebo was associated with a greater proportion of individuals with ≥5-point KCCQ overall summary improvement (42.9% vs 32.5%; AOR, 1.73; 95% CI, 0.98-3.05; P =.06) and ≥20% decrease in NT-proBNP (44% vs 29.4%; AOR, 1.9; 95% CI, 1.09-3.31; P =.02). The presence of type 2 diabetes did not significantly affect these improvements. 

Limitations to this study included an inability to detect effects on mortality or HF-related hospitalizations, a lack of assessment of benefits to HF-related health status, and potential limitations to generalizability because of the exclusive enrollment of participants in the United States.

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The study researchers concluded that, regardless of type 2 diabetes status, “the addition of dapagliflozin for 12 weeks did not affect the mean NT-proBNP” in patients with HFrEF; however, dapagliflozin was associated with an increase in “the proportion of patients experiencing clinically meaningful improvements in HF disease-specific health status and natriuretic peptides.”

Disclosure: This clinical trial was supported by AstraZeneca Pharmaceuticals LP. Please see the original reference for a full list of authors’ disclosures.


Nassif ME, Windsor S, Tang F, et al. Dapagliflozin effects on biomarkers, symptoms, and functional status in patients with heart failure with reduced ejection fraction: the DEFINE-HF trial [published online September 16]. Circulation.  doi:10.1161/CIRCULATIONAHA.119.042929