Efficacy and Safety of Dapagliflozin in Heart Failure With Reduced Ejection Fraction According to N-Terminal Pro-B-Type Natriuretic Peptide: Insights From the DAPA-HF Trial.

Abstract

BACKGROUND:

Effective therapies for HFrEF usually reduce NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, and it is important to establish whether new treatments are effective across the range of NT-proBNP.

METHODS:

We evaluated both these questions in the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial. Patients in New York Heart Association functional class II to IV with a left ventricular ejection fraction ≤40% and a NT-proBNP level ≥600 pg/mL (≥600 ng/L; ≥400 pg/mL if hospitalized for HF within the previous 12 months or ≥900 pg/mL if atrial fibrillation/flutter) were eligible. The primary outcome was the composite of an episode of worsening HF or cardiovascular death.

RESULTS:

Of the 4744 randomized patients, 4742 had an available baseline NT-proBNP measurement (median, 1437 pg/mL [interquartile range, 857-2650 pg/mL]). Compared with placebo, treatment with dapagliflozin significantly reduced NT-proBNP from baseline to 8 months (absolute least-squares mean reduction, -303 pg/mL [95% CI, -457 to -150 pg/mL]; geometric mean ratio, 0.92 [95% CI, 0.88-0.96]). Dapagliflozin reduced the risk of worsening HF or cardiovascular death, irrespective of baseline NT-proBNP quartile; the hazard ratio for dapagliflozin versus placebo, from lowest to highest quartile was 0.43 (95% CI, 0.27-0.67), 0.77 (0.56-1.04), 0.78 (0.60-1.01), and 0.78 (0.64-0.95); P for interaction=0.09. Consistent benefits were observed for all-cause mortality. Compared with placebo, dapagliflozin increased the proportion of patients with a meaningful improvement (≥5 points) in Kansas City Cardiomyopathy Questionnaire total symptom score (P for interaction=0.99) and decreased the proportion with a deterioration ≥5 points (P for interaction=0.87) across baseline NT-proBNP quartiles.

CONCLUSIONS:

In patients with HFrEF, dapagliflozin reduced NT-proBNP by 300 pg/mL after 8 months of treatment compared with placebo. In addition, dapagliflozin reduced the risk of worsening HF and death, and improved symptoms, across the spectrum of baseline NT-proBNP levels included in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.

• Authors: Jawad H Butt, Carly Adamson, Kieran F Docherty, Rudolf A de Boer, Mark C Petrie, Silvio E Inzucchi, Mikhail N Kosiborod, Anna Maria Langkilde, Daniel Lindholm, Felipe A Martinez, Olof Bengtsson, Morten Schou, Eileen O'Meara, Piotr Ponikowski, Marc S Sabatine, Mikaela Sjöstrand, Scott D Solomon, Pardeep S Jhund, John J V McMurray, Lars Køber
• Journal: Circulation. Heart failure (Circ Heart Fail) Vol. 14 Issue 12 Pg. e008837 (12 2021) ISSN: 1941-3297 [Electronic] United States
• PMID: 34802253 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzhydryl Compounds
• Glucosides
• Peptide Fragments
• pro-brain natriuretic peptide (1-76)
• Natriuretic Peptide, Brain
• dapagliflozin

Topics

• Aged
• Atrial Fibrillation (drug therapy, physiopathology)
• Benzhydryl Compounds (adverse effects, therapeutic use)
• Clinical Trials as Topic
• Glucosides (adverse effects, therapeutic use)
• Heart Failure (drug therapy, physiopathology)
• Hospitalization (statistics & numerical data)
• Humans
• Male
• Middle Aged
• Natriuretic Peptide, Brain (therapeutic use)
• Peptide Fragments (therapeutic use)
• Stroke Volume (drug effects)
• Ventricular Function, Left (drug effects)