Effects of dapagliflozin on symptoms, function and quality of life in patients with heart failure and reduced ejection fraction: results from the DAPA-HF trial

Kosiborod, M. N. et al. (2020) Effects of dapagliflozin on symptoms, function and quality of life in patients with heart failure and reduced ejection fraction: results from the DAPA-HF trial. Circulation, 141(2), pp. 90-99. (doi: 10.1161/CIRCULATIONAHA.119.044138) (PMID:31736335) (PMCID:PMC6964869)

Abstract

Background: Goals of management in patients with heart failure and reduced ejection fraction include reducing death and hospitalizations, and improving health status (symptoms, physical function, and quality of life). In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), sodium–glucose cotransporter-2 inhibitor, dapagliflozin, reduced death and hospitalizations, and improved symptoms in patients with heart failure and reduced ejection fraction. In this analysis, we examine the effects of dapagliflozin on a broad range of health status outcomes, using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Methods: KCCQ was evaluated at randomization, 4 and 8 months. Patients were divided by baseline KCCQ total symptom score (TSS); Cox proportional hazards models examined the effects of dapagliflozin on clinical events across these subgroups. We also evaluated the effects of dapagliflozin on KCCQ-TSS, clinical summary score, and overall summary score. Responder analyses were performed to compare proportions of dapagliflozin versus placebo-treated patients with clinically meaningful changes in KCCQ at 8 months. Results: A total of 4443 patients had available KCCQ at baseline (median KCCQ-TSS, 77.1 [interquartile range, 58.3–91.7]). The effects of dapagliflozin vs placebo on reducing cardiovascular death or worsening heart failure were consistent across the range of KCCQ-TSS (lowest to highest tertile: hazard ratio, 0.70 [95% CI, 0.57–0.86]; hazard ratio, 0.77 [95% CI, 0.61–0.98]; hazard ratio, 0.62 [95% CI, 0.46–0.83]; P for heterogeneity=0.52). Patients treated with dapagliflozin had greater improvement in mean KCCQ-TSS, clinical summary score, and overall summary score at 8 months (2.8, 2.5 and 2.3 points higher versus placebo; P<0.0001 for all). Fewer patients treated with dapagliflozin had a deterioration in KCCQ-TSS (odds ratio, 0.84 [95% CI, 0.78–0.90]; P<0.0001); and more patients had at least small, moderate, and large improvements (odds ratio, 1.15 [95% CI, 1.08–1.23]; odds ratio, 1.15 [95% CI, 1.08–1.22]; odds ratio, 1.14 [95% CI, 1.07–1.22]; number needed to treat=14, 15, and 18, respectively; P<0.0001 for all; results consistent for KCCQ clinical summary score and overall summary score). Conclusions: Dapagliflozin reduced cardiovascular death and worsening heart failure across the range of baseline KCCQ, and improved symptoms, physical function, and quality of life in patients with heart failure and reduced ejection fraction. Furthermore, dapagliflozin increased the proportion of patients experiencing at least small, moderate, and large improvements in health status; these effects were clinically important.

• Item Type: Articles
• Additional Information: The DAPA-HF trial was funded by AstraZeneca. Editorial support in manuscript submission was also funded by AstraZeneca.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Docherty, Dr Kieran and Jhund, Professor Pardeep and Petrie, Professor Mark and McMurray, Professor John
• Authors: Kosiborod, M. N., Jhund, P., Docherty, K. F., Diez, M., Petrie, M. C., Verma, S., Nicolau, J. C., Merkely, B., Kitakaze, M., DeMets, D. L., Inzucchi, S. E., Køeber, L., Martinez, F. A., Ponikowski, P., Sabatine, M. S., Solomon, S. D., Bengtsson, O., Lindholm, D., Niklasson, A., Sjöstrand, M., Langkilde, A. M., and McMurray, J. J.V.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Circulation
• Publisher: American Heart Association
• ISSN: 1524-4539
• ISSN (Online): 1524-4539
• Published Online: 17 November 2019
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Circulation 141(2)90-99
• Publisher Policy: Reproduced under a Creative Commons License