TY - JOUR
T1 - Efficacy and Safety of Dapagliflozin in Heart Failure With Reduced Ejection Fraction According to N-Terminal Pro-B-Type Natriuretic Peptide
T2 - Insights From the DAPA-HF Trial
AU - Butt, Jawad H
AU - Adamson, Carly
AU - Docherty, Kieran F
AU - de Boer, Rudolf A
AU - Petrie, Mark C
AU - Inzucchi, Silvio E
AU - Kosiborod, Mikhail N
AU - Maria Langkilde, Anna
AU - Lindholm, Daniel
AU - Martinez, Felipe A
AU - Bengtsson, Olof
AU - Schou, Morten
AU - O'Meara, Eileen
AU - Ponikowski, Piotr
AU - Sabatine, Marc S
AU - Sjöstrand, Mikaela
AU - Solomon, Scott D
AU - Jhund, Pardeep S
AU - McMurray, John J V
AU - Køber, Lars
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
KW - Aged
KW - Atrial Fibrillation/drug therapy
KW - Benzhydryl Compounds/adverse effects
KW - Clinical Trials as Topic
KW - Glucosides/adverse effects
KW - Heart Failure/drug therapy
KW - Hospitalization/statistics & numerical data
KW - Humans
KW - Male
KW - Middle Aged
KW - Natriuretic Peptide, Brain/therapeutic use
KW - Peptide Fragments/therapeutic use
KW - Stroke Volume/drug effects
KW - Ventricular Function, Left/drug effects
UR - http://www.scopus.com/inward/record.url?scp=85122325376&partnerID=8YFLogxK
U2 - 10.1161/CIRCHEARTFAILURE.121.008837
DO - 10.1161/CIRCHEARTFAILURE.121.008837
M3 - Journal article
C2 - 34802253
SN - 1941-3289
VL - 14
SP - 1305
EP - 1318
JO - Circulation. Heart failure
JF - Circulation. Heart failure
IS - 12
ER -