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.


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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.

Reference

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