Background: Goals of management in patients with heart failure and reduced ejection
fraction (HFrEF) include reducing death and hospitalizations, and improving health
status (symptoms, physical function and quality of life). In the Dapagliflozin And
Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial, sodium-glucose cotransporter-2
inhibitor, dapagliflozin, reduced death and hospitalizations, and improved symptoms
in patients with HFrEF. 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 (CSS)
and overall summary score (OSS). Responder analyses were performed to compare proportions
of dapagliflozin vs. placebotreated patients with clinically meaningful changes in
KCCQ at 8 months. Results: 4443 patients had available KCCQ at baseline (median KCCQ-TSS
77.1 [IQR 58.3-91.7]). The effects of dapagliflozin versus placebo on reducing cardiovascular
death or worsening HF were consistent across the range of KCCQ-TSS (lowest to highest
tertile: HR (95% CI) 0.70 (0.57-0.86); 0.77 (0.61-0.98); 0.62 (0.46-0.83); P for heterogeneity=0.52).
Patients treated with dapagliflozin had greater improvement in mean KCCQ-TSS, -CSS
and - OSS at 8 months (2.8, 2.5 and 2.3 points higher vs. placebo; P <0.0001 for all).
Fewer patients treated with dapagliflozin had a deterioration in KCCQ-TSS (OR 0.84,
95% CI 0.78-0.90; P<0.0001); and more patients had at least small, moderate and large
improvements (OR, 95% CI: 1.15, 1.08-1.23; 1.15 (1.08-1.22); 1.14 (1.07-1.22); number-needed-to-treat=14,
15 and 18, respectively; P<0.0001 for all; results consistent for KCCQ-CSS and -OSS).
Conclusions:Dapagliflozin reduced cardiovascular death and worsening HF across the
range of baseline KCCQ, and improved symptoms, physical function and quality of life
in patients with HFrEF. 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://clinicaltrials.gov;
Unique Identifier: NCT03036124.
