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
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | e008837 |
| Tidsskrift | Circulation: Heart Failure |
| Vol/bind | 14 |
| Udgave nummer | 12 |
| Sider (fra-til) | 1305-1318 |
| Antal sider | 14 |
| ISSN | 1941-3289 |
| DOI | |
| Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:
The DAPA-HF trial (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) was funded by AstraZeneca. Dr McMurray was supported by British Heart Foundation Centre of Research Excellence grant RE/18/6/34217.
Funding Information:
Dr Schou reports compensation from Novo Nordisk AS for other services; compensation from AstraZeneca for other services; and compensation from Boehringer Ingelheim for other services. Dr O’Meara reports compensation from AstraZeneca for consultant services; compensation from Canadian Cardiovascular Society for consultant services; and compensation from Canadian Cardiovascular Society for other services. Dr Ponikowski reports compensation from AstraZeneca for consultant services; compensation from Boehringer Ingelheim for consultant services; compensation from Servier for consultant services; compensation from AstraZeneca for other services; compensation from Pfizer for other services; compensation from Amgen for consultant services; compensation from Vifor Pharma for consultant services; compensation from Novartis for other services; and compensation from Abbott Vascular for other services. Dr Sabatine reports research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Daiichi-Sankyo, Eisai, Intarcia, IONIS, Medicines Company, MedImmune, Merck, Novartis, Pfizer, and Quark Pharmaceuticals; and consulting for Althera, Amgen, Anthos Therapeutics, AstraZeneca, Bristol-Myers Squibb, CVS Caremark, DalCor, Dr Reddy’s Laboratories, Fibrogen, IFM Therapeutics, Intarcia, MedImmune, Merck, Moderna, and Novo Nordisk. Dr Sjöstrand reports employment by AstraZeneca. Dr Solomon reports compensation from GlaxoSmithKline for consultant services; grants from Theracos; grants from Celladon Corporation; grants from Bristol-Myers Squibb; grants from GlaxoSmithKline; compensation from Arena for consultant services; stock options in Dinaqor; grants from Amgen; compensation from Novartis for consultant services; compensation from Quantum Genomics for consultant services; compensation from Bayer for consultant services; compensation from Bristol-Myers Squibb for consultant services; grants from Respicardia, Inc; compensation from cardior for consultant services; grants from Novo Nordisk; compensation from Cytokinetics for consultant services; grants from Bayer; compensation from Sarepta Therapeutics, Inc. for consultant services; compensation from Action Medical Research for consultant services; grants from AstraZeneca; compensation from Tremeau for consultant services; compensation from Theracos for consultant services; grants from Mesoblast; grants from Myokardia; compensation from Moderna for consultant services; compensation from Akros for consultant services; grants from Actelion Pharmaceuticals; compensation from Amgen for consultant services; compensation from Boehringer Ingelheim for consultant services; compensation from Alnylam Pharmaceuticals for consultant services; grants from Alnylam Pharmaceuticals; grants from Bellepheron; compensation from Roche Diagnostics Corporation for consultant services; compensation from American Regent for consultant services; travel support from Corvia; compensation from AstraZeneca for consultant services; compensation from cardurion for consultant services; compensation from Merck for consultant services; grants from Ionis; grants from Sanofi Pasteur Inc; compensation from Daiichi Sankyo Company for consultant services; compensation from Myokardia for consultant services; grants from Neurotronik; grants from Cytokinetics; compensation from Sanofi Pasteur Inc for consultant services; grants from Eli Lilly and Company; compensation from Abbott Vascular for consultant services; grants from Novartis; compensation from Eli Lilly and Company for consultant services; compensation from Johnson and Johnson for consultant services; compensation from CellProThera for consultant services; compensation from tenaya for consultant services; grants from Eidos; and compensation from Cardiac Dimensions for consultant services. Dr Jhund reports compensation from Novo Nordisk AS for consultant services; compensation from Novartis for consultant services; compensation from AstraZeneca for consultant services; and compensation from Boehringer Ingelheim for consultant services. Dr McMurray reports grants from AstraZeneca. Dr Køber reports compensation from Novartis for other services; compensation from Novo Nordisk for other services; and compensation from AstraZeneca for other services. The other authors report no conflicts.
Funding Information:
K.F. Docherty reports compensation from AstraZeneca for other services. Dr de Boer reports grants from Cardior Pharmaceuticals GmbH to other; compensation from Novartis for other services; compensation from AstraZeneca for other services; grants from AstraZeneca to other; grants from Ionis Pharmaceuticals, Inc. to other; compensation from Roche Diagnostics GmbH for other services; grants from Roche Diagnostics GmbH to other; compensation from Bayer for other services; grants from Boehringer Ingelheim to other; grants from Novo Nordisk to other; compensation from Abbott Fund for other services; and grants from Abbott Fund to other. M.C. Petrie reports compensation from Bayer for end point review committee services; compensation from Boehringer Ingelheim for end point review committee services; compensation from Boehringer Ingelheim for consultant services; compensation from AstraZeneca for consultant services; compensation from Novo Nordisk for consultant services; compensation from Takeda California, Inc for end point review committee services; compensation from Novo Nordisk for consultant services; grants from Boehringer Ingelheim; compensation from Novo Nordisk for end point review committee services; compensation from Novartis for consultant services; grants from Novartis to other; grants from SQ Innovation to other; compensation from SQ Innovation for consultant services; and grants from AstraZeneca to other. Dr Inzucchi reports compensation from Merck for consultant services; compensation from Lexicon Pharmaceuticals, Inc. for consultant services; compensation from AstraZeneca for consultant services; compensation from Boehringer Ingelheim for consultant services; compensation from Abbott Diabetes Care for consultant services; compensation from VTV Therapeutics for consultant services; travel support from Novo Nordisk; compensation from AstraZeneca for other services; compensation from Boehringer Ingelheim for other services; travel support from Boehringer Ingelheim; travel support from AstraZeneca; compensation from Novo Nordisk for consultant services; and compensation from Esperion for consultant services. Dr Kosiborod reports compensation from Novo Nordisk for consultant services; compensation from Applied Therapeutics for consultant services; compensation from Janssen Global Services, LLC for consultant services; grants from Boehringer Ingelheim; compensation from AstraZeneca for consultant services; compensation from Eli Lilly and Company for consultant services; grants from AstraZeneca; compensation from Merck for consultant services; compensation from Bayer for consultant services; compensation from Amgen for consultant services; compensation from Sanofi US Services Inc for consultant services; compensation from Boehringer Ingelheim for consultant services; and compensation from Vifor Pharma for consultant services. Dr Langkilde reports stock holdings in AstraZeneca and employment by AstraZeneca. Dr Lindholm reports employment by AstraZeneca. O. Bengtsson reports employment by AstraZeneca AB.
Publisher Copyright:
© 2021 American Heart Association, Inc.
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