Efficacy And Safety Of Tolvaptan For The Treatment Of Heart Failure:A Meta-Analysis

BackgroundHeart failure is a condition in which the heart cannot eject sufficient blood to meet the oxygen requirements of peripheral tissues,and is often associated with symptoms caused by fluid retension.As a nonpeptide competitive oral vasopressin V2-receptor antagonist(VRA),tolvaptan is expected to promote an increase in the clearance of free water and to exert further diuresis to improve volume overload without the deterioration of serum electrolytes or renal function.We performed a meta-analysis of published studies to systematically measure the efficacy and safety of tolvaptan for the treatment of heart failure.Objective(1)To systematically measure the efficacy of tolvaptan for the treatment of heart failure.(2)To systematically measure the safety of tolvaptan for the treatment of heart failure.MethodsWe searched Medline and PubMed to retrieve studies using the following search terms:"receptors,vasopressin”,"tolvaptan”,and"heart failure”.The screening of relevant abstracts,the selection of studies,and the extraction of data were performed independently by two of the authors,and conflicts were resolved through consensus and arbitration by a third author.The involved trials’quality was assessed by the risk of bias summary.All analyses were performed on Stata version 14.Heterogeneity was estimated by the I~2 index.Publication bias was assessed using Begg’s funnel plots and Egger’s test.Results(1)Using of tolvaptan result in a decrease of body weight at a level of-0.860 kg(95%CI,-0.996,-0.724)(P=0.00),an increase of urine volume to a level of 1.697 L(95%CI,1.429,1.966)(P<0.001),a 1.218-fold(95%CI,1.085,1.368)remission of edema(P=0.001).(2)Using of tolvaptan may not result in the hemodynamic changes like heart rate(0.261[95%CI,-1.343,1.866],P=0.750),systolic blood pressure(0.448[95%CI,-1.115,2.011],P=0.574),and diastolic blood pressure(-0.253[95%CI,-1.995,1.488],P=0.776).(3)By meta-analysis,6.063%(95%CI,4.334,8.480)more patients in the tolvaptan-treated group had isohydria disorders like peripheral edema,thirst,dry mouth,or dehydration than in the control group(P=0.00).Similarly,5.737%(95%CI,2.344,14.040)more patients in the tolvaptan-treated group developed urinary tract disorders like urinary frequency or polyuria than in the control group(P=0.00).No statistical differences existed for other adverse events like cardiac disorders,digestive system disorders,nervous system disorders,infection,renal disorders,hyperuricemia,hyperkalemia,or hypernatremia.(4)Using of tolvaptan may not reduct the mortality of heart failure(OR:0.881[95%CI:0.629-1.232];P=0.458).Conclusion(1)Tolvaptan has the potential to improve congestive signs from volume overload in the treatment of heart failure.(2)Tolvaptan may not result in deteriorating hemodynamics regulation and any serious adverse events.(3)Tolvaptan can not reduce mortality in heart failure.