SGLT-2 inhibitors on prognosis and health-related quality of life in patients with heart failure and preserved ejection fraction: A systematic review and meta-analysis

Background: Heart failure with preserved ejection fraction (HFpEF) is becoming the main subtype of heart failure, but lacks proven effective therapies. Sodium-glucose cotransporter-2 (SGLT-2) inhibitor, a new kind of oral glucose-lowering agent, shows a great effect on improving cardiovascular outcomes. Based on the results of current RCTs, we perform this meta-analysis to illustrate the therapeutic impact of SGLT2i in HFpEF patients. Methods: We systematically searched the online database and 10 RCTs were involved. The primary outcome was the prognosis outcome of HFpEF patients, including a composite outcome of cardiovascular (CV) death and hospitalization for heart failure (HHF), CV mortality, HHF, and all-cause mortality. Main secondary outcomes included improvement of KCCQ-TSS (Kansas City Cardiomyopathy Questionnaire and total symptom score) and 6-Minute Walk Test (6MWT). All pooled results were calculated by the random-effects model. Statistical heterogeneity was assessed using the chi-squared test and was quantified using the I-squared statistic. Results: Ten RCTs comprising 10,334 patients were involved in. Incidence of composite outcome was reduced in SGLT-2 inhibitor group compared with placebo (HR: 0.78, 95% CI: 0.69-0.88, p = 0.00). Improvement of KCCQ-TSS was also more pronounced in the SGLT-2 inhibitor group (MD: 2.74, 95% CI: 1.30-4.18, p = 0.00). No statistical difference was observed in 6MWT. Conclusion: Treating HFpEF patients with SGLT-2 inhibitors is associated with reducing the composite outcome of CV death and HHF and improving health-related quality of life. Further studies with more evidence are in need to confirm this conclusion.