Sex-related differences in health-related quality-of-life measured using the EuroQol 5-Dimension questionnaire across the LVEF spectrum in DAPA-HF and DELIVER

Although sex-related differences in response to disease-specific health-related quality-of-life (HRQL) instruments such as the KCCQ have been investigated in patients with heart failure (HF), this is not the case for generic HRQL instruments.

To assess the sex-specific differences in health status measured using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) in patients with HF with reduced and mildly reduced or preserved ejection fraction (HFrEF and HFmrEF/HFpEF), and to assess the effect of dapagliflozin on EQ-5D-5L index scores.

Using patient-level data from the DAPA-HF and DELIVER trials comparing dapagliflozin to placebo, we analysed patient-reported outcomes for each dimension of the EQ-5D index scores between men and women. The 5 dimensions of the descriptive section of the EQ-5D-5L include mobility ("walking around"), self-care ("washing or dressing self"), usual activities ("e.g., work, study, housework, family or leisure activities"), pain/discomfort ("pain or discomfort"), and anxiety/depression ("anxious or depressed"). Each dimension is divided into 5 levels (1-5) i.e., no problem, slight problem, moderate problem, severe problem, and extreme problem (cannot do activity/extreme symptom).

Of 4744 patients with HFrEF, 4390 completed the EQ-5D-5L index scores (3408 men and 982 women, 77.6% vs. 22.4%). The correresponding numbes in 6263 patients with HFmrEF/HFpEF were 5745 overall and 3320 men vs. 2425 women (57.8% vs. 42.2%). Regardless of HF phenotype, women had significantly worse (lower) baseline index scores overall compared to men (0.849 vs. 0.899 in HFrEF and 0.844 vs. 0.884 in HFmrEF/HFpEF, both p<0.001). Although scores varied markedly by question, women generally had worse health status in all the dimensions as compared with men in patients with HFrEF (39% vs. 29% reporting a moderate or greater problem for mobility, 17% vs. 9% for self-care, 36% vs. 25% for usual activities, 29% vs. 19% for pain/discomfort, and 21% vs. 13% for anxiety/depression, all p<0.001) (Figure, top panel). A broadly similar pattern was observed in HFmrEF/HFpEF (Figure, bottom panel). In all patients, across the range of LVEF, there dapagliflozin led to a significant placebo corrected increase (improvement) in index score (0.008, 95% CI 0.002 to 0.014), with no interaction between sex and the effect of dapagliflozin (p for interaction with sex = 0.50).

Women reported significantly poorer health status in both HFrEF and HFmrEF/HFpEF compared to men. Dapagliflozin treatment improved EQ-5D index scores irrespective of sex across the range of ejection fraction.

Sex differences in the distribution of responses to EQ-5D-5L questionnaire. EQ-5D-5L, EuroQol 5-Dimension 5-Level questionnaire; HFmrEF, heart failure with mildly reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction.