A Meta-analysis Of SGLT2 Inhibitors In Patients With Heart Failure With Or Without Diabetes

Backgroud:HF is a clinical syndrome characterized by typical symptoms(e.g.breathlessness,ankle swelling and fatigue)that may be accompanied by signs(e.g.elevated jugular venous pressure,pulmonary crackles and peripheral oedema)caused by a structural and/or functional cardiac abnormality,resulting in a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress.It is a serious and terminal stage of a variety of cardiovascular diseases and an important part of the global prevention and treatment of chronic cardiovascular diseases.Recently,a new class of oral hypoglycemic agents,sodium-glucose transporter 2 inhibitors,have been found to prevent cardiovascular events,particularly by reducing the risk of cardiovascular death or heart failure hospitalization.We aimed to estimate the cardiovascular protective effect and safety outcomes of SGLT2 inhibitors in all randomly assigned patients with HF and in relevant subgroups from inclusive trails.Methods:In this systematic review and meta-analysis,according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,we searched PUBMED,Sciencedirect,The cochrane library,Ovid MEDLINE,Web of science,Scopus,Embase,CNKI for data from prospective randomized controlled trials assessing the effects of SGLT2 treatment compared with controls.The primary outcome was a composite of cardiovascular death or hospitalization for heart failure.Second outcomes were cardiovascular death,hospitalization for heart failure,death from all cause.Additionally,we assessed the effects of treatment in prespecified subgroups on the combined risk of cardiovascular death or hospitalization for heart failure.These subgroups were based on age,sex,race,baseline diabetes status,baseline NYHA class,estimated GFR and BMI at baseline.We estimated summary relative risks with fixed effects meta-analysis,with the I~2statistic used to estimate heterogeneity of results beyond chance.Findings:Among 20252 patients combined from all 8 trails,SGLT2 inhibitors were accompanied by a 28%relative reduction in the combined risk of cardiovascular death of heart failure hospitalization(HR 0.72;[95%CI 0.67-0.77];P<0.00001),and by a 34%decrease in heart failure hospitalization(0.66[0.61-0.72];P<0.00001),a 13%decrease in cardiovascular death(0.87[0.79-0.96];P=0.007),a 10%decrease in all cause death(0.90[0.83-0.97];P=0.008).All tests for heterogeneity of effect size between trials were not significant.The pooled treatment effects showed consistent benefits for subgroups based on age,sex,baseline diabetes status,estimated GFR and BMI at baseline,but suggested treatment-by-subgroup interactions for subgroups based on race and baseline NYHA class.Interpretation:SGLT2 inhibition was associated with a decreased risk of cardiovascular death or heart failure hospitalization and also improving renal outcomes and reducing all-cause death,especial of hospitalization for reduced ejection fraction heart failure.