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

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.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03036124.

Keywords: health status; heart failure; outcome; sodium-glucose transporter 2 inhibitors.

Figure 1.

Time to first event of cardiovascular death or worsening heart failure according to KCCQ-TSS tertile at randomization. Tertile >87.5: referent; tertile 65.7–87.5: HR, 1.30 (95% CI, 1.08–1.56), P=0.006; tertile ≤65.6: HR, 1.93 (95% CI, 1.62–2.30), P<0.001. HR indicates hazard ratio; KCCQ, Kansas City Cardiomyopathy Questionnaire; and TSS, total symptom score.

Figure 2.

Effects of dapagliflozin as compared with placebo on the clinical events across the tertiles of KCCQ-TSS at baseline. HR indicates hazard ratio; KCCQ, Kansas City Cardiomyopathy Questionnaire; and TSS, total symptom score.

Figure 3.

Effects of dapagliflozin compared with placebo on KCCQ scores over 8 months. Effects of dapagliflozin as compared with placebo on mean (A) KCCQ-TSS, (B) KCCQ-CSS, and (C) KCCQ-OSS over 8 months of treatment. Analysis includes those patients that are alive at the time of the KCCQ assessment (ie, 4 months and 8 months). CSS indicates clinical summary score; KCCQ, Kansas City Cardiomyopathy Questionnaire; OSS, overall summary score; and TSS, total symptom score.

Figure 4.

Responder analyses of clinically meaningful change in KCCQ at 8 months with dapagliflozin versus placebo. Responder analyses of clinically meaningful changes in (A and B) KCCQ-TSS, (C and D) KCCQ-CSS, and (E and F) KCCQ-OSS with dapagliflozin vs placebo at 8 months. Deaths are treated as not improved or as deteriorated (for the improvement and deterioration calculations, respectively). CSS indicates clinical summary score; Dapa, dapagliflozin; KCCQ, Kansas City Cardiomyopathy Questionnaire; NNT, number needed to treat (numbers in parentheses represent 95% CIs); OR, odds ratio; OSS, overall summary score; and TSS, total symptom score.