The effect of SGLT2 inhibitors on health status in patients with heart failure: a systematic review and meta-analysis

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to improve health status in patients with heart failure (HF). We aim to evaluate the effect of SGLT2i on health status [by Kansas City Cardiomyopathy Questionnaire (KCCQ)] and if effect varied by ejection fraction (EF). Randomized clinical trials of SGLT2i in patients with HF till November 2022 were assessed. Change in KCCQ total symptom score (TSS), clinical summary score (CSS), and overall summary score (OSS) from baseline to 12-16 weeks, 32 weeks, and 52 weeks follow-up were assessed. Weighted mean differences (MD) in scores and odds ratios (OR) were pooled using a random-effects model. Twelve trials (n=23,679) were included. SGLT2i significantly improved KCCQ-TSS at 12-16 weeks [MD 2.16 (1.67, 2.65); p<0.001], 32 weeks [MD 1.98 (1.43, 2.54); p<0.001] and 52 weeks [MD 1.94 (1.19, 2.69); p<0.001] follow-up. At 12-16 weeks, patients treated with SGLT2i had significantly higher odds of KCCQ-TSS improvement by ≥5 points [OR 1.27 (1.16, 1.39); p<0.001], ≥10 points [OR 1.21 (1.11, 1.32); p<0.001] and ≥15 points [OR 1.23 (1.14, 1.33); p<0.001]. Similar results were observed at mid- and long-term follow-up, and for CSS and OSS. For all analyses, findings were consistent between patients with HF with reduced or preserved EF, acute/worsening or chronic HF, and which SGLT2i used (p-interaction >0.20 for all). SGLT2i improve health status in patients with HF, with consistent and sustained benefits across all summary scores and HF subtypes. Treatment benefits were apparent within months of initiation and sustained to at least 1 year.