November 22, 2021Circulation Heart FailureOpen Access

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

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Why the study?

Effective therapies for HFrEF usually reduce NT-proBNP levels, and it is important to establish whether new treatments are effective across the range of NT-proBNP.

Does dapagliflozin reduce worsening HF or cardiovascular death in patients with HFrEF across the spectrum of baseline NT-proBNP levels?

Structured PICO

Does dapagliflozin reduce worsening HF or cardiovascular death in patients with HFrEF across the spectrum of baseline NT-proBNP levels?

Population

4,744 patients with HFrEF (NYHA class II to IV, LVEF ≤40%, NT-proBNP ≥600 pg/mL [≥400 pg/mL if hospitalized for HF within the previous 12 months or ≥900 pg/mL if atrial fibrillation/flutter])

Intervention

Dapagliflozin

Comparator

Placebo

Outcome

Composite of an episode of worsening HF or cardiovascular deathcomposite

Dapagliflozin provides consistent clinical benefits and symptom improvement in HFrEF patients regardless of their baseline NT-proBNP levels, while also significantly lowering NT-proBNP.

Implication

Supports dapagliflozin use in HFrEF irrespective of NT-proBNP levels; confirms consistent benefit and biomarker reduction in RCT.

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.