Efficacy Of ARNI,SGLT2i Alone And Combined In The Treatment Of Chronic Heart Failure:A Network Meta-analysis

Background and purpose:Heart Failure（HF）is a common and frequent clinical disease.With the continuous improvement of medical care in China,the prolongation of chronic disease survival and the aging of the population,the prevalence of heart failure in China continues to increase^[1],which has seriously affected the health of our population.A large number of clinical trials have demonstrated that ARNI and SGLT2i can benefit patients with heart failure,improve prognosis and reduce re-hospitalisation rates and mortality in heart failure patients.However,there is still lack of head-to-head meta-analysis of the efficacy of ARNI and SGLT2i alone and in combination in the treatment of chronic heart failure,and it is not possible to directly determine the efficacy of these two new anti-heart failure drugs and their combination in improving chronic heart failure.This study intends to use mesh meta-analysis to evaluate the effects of ARNI and SGLT2i alone and in combination on chronic heart failure,so as to provide a certain reference basis for the clinical drug selection of chronic heart failure.Method:We searched Pub Med,Embase,The Cochrane Library,CNKI,Wanfang and other databases.The literature search time range was from the establishment of the library until 31 December 2022.Randomized controlled trials on the efficacy of ARNI and SGLT2i in the treatment of patients with heart failure were retrieved.According to the inclusion and exclusion criteria,two researchers screened the literature and extracted relevant data from RCTs（randomized controlled trials）studies that met the inclusion criteria.Cochrane was used to conduct bias risk assessment.After quality assessment,statistical analysis was performed using Revman5.3 and Stata17.0.Result:A total of 7 RCTS were included,including 29,387 patients.The control group received conventional treatment（such as diuretics,vasodilators,angiotensin-converting enzyme inhibitors,beta-blockers,etc.）,and the experimental group received appropriate doses of ARNI,SGLT2i,and ARNI combined with SGLT2i.1.The results of conventional meta-analysis showed that（1）The Heart Failure hospitalization rate:the trial group（14.89%）was lower than the control group（19.12%）,RR=0.76,95%CI（0.70,0.82）,P<0.00001;（2）cardiovascular mortality:the trial group（9.97%）was lower than the control group（11.58%）,RR=0.86,95%CI（0.81,0.92）,P<0.00001;（3）all-cause mortality:lower in the trial group（14.23%）than in the control group（15.71%）,RR=0.91,95%CI（0.86,0.96）,P=0.0004<0.05;（4）The incidence of compound outcome（recurrent HF hospitalization combined with cardiovascular death）:the trial group（19.57%）was lower than that of the control group（24.85%）,RR=0.79,95%CI（0.75,0.83）,P<0.00001;（5）Incidence of serious adverse events:the test group（10.81%）was lower than that of the control group（11.94%）RR=0.91,95%CI（0.85,0.97）,P=0.004;（P<0.05 in the above results was statistically significant between the two groups.）2.The results of mesh meta-analysis comparing each intervention are as follows:（1）Comparison of hospitalization rates for heart failure:Compared with placebo,Dapagliflozin（RR=0.65,95%CI:0.49,0.86）,Empagliflozin（RR=0.69,95%CI:0.52,0.92）,Sotagliflozin（RR=0.51,95%CI:0.33,0.79）,Sacubitril/Valsartan（RR=0.92,95%CI:0.73,0.98）,Sacubitril/Valsartan combined with Dapagliflozin（RR=0.82,95%CI:0.46,0.91）can effectively reduce cardiovascular mortality in patients with chronic heart failure,and the difference in the above comparison results was statistically significant.Indirect comparison showed that there was no significant difference in hospitalization rate of heart failure between SGLT2i,between SGLT2i and ARNI,or between single drug and combination.Sucras were ranked in descending order:Placebo（90.2%）,Sacubitril/Valsartan（78.5%）,Sacubitril/Valsartan and Dapagliflozin（55.5%）,Empagliflozin（38.7%）,Dapagliflozin（29.0%）,and Sotagliflozin（8.2%）.（2）Comparison of cardiovascular mortality:Compared with placebo,Dapagliflozin（RR=0.82,95%CI:0.71,0.93）,Sacubitril/Valsartan（RR=0.81,95%CI:0.74,0.90）,Sacubitril/Valsartan combined with Dapagliflozin（RR=0.58,95%CI:0.36,0.95）can effectively reduce cardiovascular mortality in patients with chronic heart failure,and the difference in the above comparison results was statistically significant.Indirect comparison showed that there was no significant difference in hospitalization rate of heart failure between SGLT2i,between SGLT2i and ARNI,or between single drug and combination.SUCRA was ranked in descending order:placebo（93.1%）,Empagliflozin（66.2%）,Sotagliflozin（57.3%）,Dapagliflozin（39.1%）,Sacubitril/Valsartan（37.3%）,Sacubitril/Valsartan combined with Dapagliflozin（7.0%）.（3）Comparison of all-cause mortality:Compared with placebo,Dapagliflozin（RR=0.82,95%CI:0.72,0.93）,Sacubitril/Valsartan（RR=0.88,95%CI:0.74,0.97）,Sacubitril/Valsartan combined with Dapagliflozin（RR=0.68,95%CI:0.44,0.82）can reduce all-cause mortality,and the difference between the above comparison results was statistically significant.Indirect comparison showed no significant difference in all-cause mortality between SGLT2i,between SGLT2i and ARNI,or between single drug and combination.SUCRA was ranked in descending order:placebo（90.9%）,Empagliflozin（77.2%）,Sotagliflozin（45.3%）,Sacubitril/Valsartan（45.1%）,Dapagliflozin（31.6%）,Sacubitril/Valsartan combined with Dapagliflozin（9.9%）.（4）Comparison of the incidence of combined outcomes（recurrent HF hospitalization combined with cardiovascular death）:Compared with placebo,Dapagliflozin（RR=0.67,95%CI:0.52,0.87）and Empagliflozin（RR=0.76,95%CI:0.58,0.98）reduced the incidence of multiple outcomes,and the difference was statistically significant.Indirect comparisons showed that Dapagliflozin（RR=1.42,95%CI:1.01,2.02）reduced the incidence of compound outcomes compared with Sacubitril/Valsartan,there was no significant difference in all-cause mortality among other indirect comparisons.SUCRA was ranked in order from large to small:placebo（84.3%）,Sacubitril/Valsartan（75.0%）,Sotagliflozin（58.1%）,Empagliflozin（35.3%）,Sacubitril/Valsartan combined with Dapagliflozin（30.0%）,Dapagliflozin（17.3%）.（5）Comparison of the incidence of serious adverse events:Analysis results showed that there was no statistically significant difference in the outcome between treatments.Conclusion:1.In the hospitalization rate of heart failure,Dapagliflozin,Empagliflozin,Sotagliflozin,Sacubitril/Valsartan,Sacubitril/Valsartan combined with Dapagliflozin can reduced the hospitalization rate of heart failure compared with placebo.There was no significant difference between the interventions.2.In terms of cardiovascular death and all-cause mortality,compared with placebo,Dapagliflozin,Sacubitril/Valsartan,Sacubitril/Valsartan combined with Dapagliflozin could reduce the incidence of cardiovascular death and all-cause death in patients with chronic heart failure,and the difference was statistically significant.There was no significant difference between the interventions.3.In terms of the incidence of compound outcome（hospitalization with recurrent HF combined with cardiovascular death）,Dapagliflozin and Empagliflozin could reduce the incidence of compound outcome compared with placebo,and the difference was statistically significant.Comparison among interventions showed that Dapagliflozin could reduce the incidence of compound outcome compared with Sacubitril/Valsartan,but there was no statistically significant difference among other interventions.4.In terms of the occurrence of serious adverse reactions,the analysis results showed that there was no statistical significance in the results between treatments.