SGLT2 inhibitors and health-related quality of life in heart failure: a systematic review and meta-analysis
C Di Lorenzo, G D Femminella, L A Ceparano, F Manfredonia, L de Lisio, K Komici, G RengoAbstract
Background
Health-related quality of life (HR-QoL) is a crucial patient-centered outcome that is substantially impaired in chronic conditions such as heart failure (HF). Although sodium–glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated robust efficacy in reducing cardiovascular mortality and HF hospitalizations across the left ventricular ejection fraction (LVEF) spectrum, a comprehensive and quantitative synthesis defining the precise magnitude of their effect on patient-reported outcomes—particularly the Kansas City Cardiomyopathy Questionnaire (KCCQ) score—remains essential to further optimize patient-centered care.
Objective
The aim of the present study was to systematically quantify the treatment effect of SGLT2i on HR-QoL, as measured by changes in the KCCQ score from baseline, and to assess the consistency of this therapeutic effect across distinct HF phenotypes.
Methods
A meta-analysis of randomized controlled trials of HF patients treated with SGLT2i was performed. The primary endpoint was the mean change from baseline in the KCCQ score. Data were pooled using an inverse-variance weighted random-effects model to account for anticipated between-study heterogeneity. Effect estimates were expressed as mean differences (MD) with corresponding 95% confidence intervals (CIs). Statistical heterogeneity was quantified using the I² statistic and Cochran’s Q test. Subgroup analyses were conducted according to HF phenotype: overall HF population, HF with reduced ejection fraction (HFrEF, LVEF≤40%), and HF with preserved ejection fraction (HFpEF, LVEF>40%).
Results
The pooled analysis included 10560 patients. In the overall population, treatment with SGLT2i was associated with a significant improvement in KCCQ score compared with baseline (MD 9.78; 95% CI 7.42–12.15; p<0.00001), although substantial heterogeneity was observed (I²=97%; p<0.00001). Subgroup analyses demonstrated consistent HR-QoL benefits across HF phenotypes: the overall HF cohort (n=1,027) showed an MD of 21.11 (95% CI 6.10–36.12; I²=99%); the HFrEF cohort (n=2,714) an MD of 7.18 (95% CI 4.25–10.11; I²=92%); and the HFpEF cohort (n=6,819) an MD of 8.06 (95% CI 5.77–10.34; I²=85%). Importantly, the test for subgroup differences was not statistically significant (p=0.20; I²=38.0%), indicating that the magnitude of symptomatic benefit was consistent across the LVEF spectrum.
Conclusions
SGLT2i are associated with a statistically robust and clinically meaningful improvement in HR-QoL in patients with HF. This benefit appears consistent across the entire ejection fraction spectrum, supporting the role of SGLT2i as a phenotype-independent cornerstone of contemporary pharmacological management in HF.