Perioperative Anticoagulants Management Of Endoscopic Resection And Post-procedural Bleeding: A Research Of Evidence-based Medicine

In recent years,polypectomy,endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD),have been widely used by endoscopists.With the surgery become more and more complex,and endoscopists have gradually begun to pay attention to its complications,among which post-procedural bleeding(PPB)is one of the most important complications.According to the guidelines published by the endoscopic associations,endoscopic resection itself is a kind of operation with highrisk or ultra high risk for PPB,so it is particularly important to prevent and manage PPB.The use of anticoagulants is considered to be an independent risk factor for PPB.Warfarin and direct oral anticoagulants(DOACs)are the main representatives of anticoagulants.DOACs,in particular,are increasingly favored by clinicians because of their stable pharmacodynamics.However,studies have also shown DOACs may significantly increase the risk of gastrointestinal bleeding.At present,several clinical studies have compared the effects of DOACs and warfarin,but the results of these evidences are not consistent.Evidence-based medical studies are needed to summarize and analyze the effects of the two on endoscopic resection of PPB.For management strategies of DOACs and warfarin in endoscopic resection,such as whether to stop drug,whether to use heparin bridge(HB),the guidelines issued by various national and regional digestive endoscopy societies are not unified.Therefore,there is an urgent need for evidence-based medical studies on the management strategies of different anticoagulants during perioperative of endoscopic resection,so as to help doctors make clinical decisions and provide evidence for guideline-making experts.Based on the above background,we put forward the following clinical questions: 1.Is the risk of PPB in endoscopic resection of patients taking DOACS lower than that of warfarin? 2.What is the influence of different management strategies of these two anticoagulants on PPB during perioperative period?Based on the above problems,this study adopted evidence-based medical methodology to conduct a comprehensive retrieval of the literatures,analyze the characteristics of the literatures,summarize the rules of the literatures,and use Newcastle-Ottawa Scale(NOS)to evaluate the quality of the literatures,so as to comprehensively understand the research status and quality in this field.At the same time,odds ratio(OR)data from the literatures were pooled to compare the risk of PPB and thromboembolism for DOACs and warfarin after endoscopic resection.Cumulative meta-analysis and trend test were used to analyze the trend with the cumulation of publication year and sample size.At the same time,subgroup analysis was conducted for different endoscopic resection,lesion site and DOACs' types.For the perioperative management strategies of anticoagulants,head-to-head traditional meta-analysis and network meta-analysis based on the Bayesian framework were used respectively to compare the consistency of the results and enhance the strength of the evidence,and the rank probability diagram was used to rank the management strategies of anticoagulants,so as to select the best strategies.Finally,sensitivity analysis,metaregression and funnel plots were used to analyze the heterogeneity,stability,confounding factors and publication bias and the credibility of the evidence was evaluated.Using the above methods,we obtained the following results:1.A total of 30 literatures were included after a systematic literature search.Literature analysis shows that in terms of perioperative anticoagulants and their management strategies for endoscopic resection,90% of studies are mainly conducted by Japanese scholars,and 73.33% of the studies have been published after 2018.The management strategies of perioperative anticoagulants used in various studies were different.Only 5 studies explicitly mentioned following the guidelines issued by the Japanese Society of Endoscopy.The total quality assessment score of all included literatures ranged from 5 to 8 points,with an average of 6.67 points,which indicates that the quality of the included literatures is acceptable.2.By extracting data from the literature,it was found that 586 patients in the DOACs group and 1782 patients in the warfarin group experienced PPB after endoscopic resection.The PPB rate in the DOACs group was significantly lower than that in the warfarin group(OR=0.867,95%CI: 0.771-0.975;P=0.017,I2=1.6%).The results did not change significantly after excluding studies with low quality,studies from non-Japanese scholars,and studies with small sample studies.Subgroup analysis showed that for ESD,the PPB rate of DOACs was significantly lower than that of the warfarin group(OR=0.786;95% CI: 0.633-0.976;P=0.029,I2=0%).There were no statistical differences in other endoscopic resection methods,lesion sites and types of DOACs.3.With the accumulation of publication time and sample size,we found that the PPB rate after endoscopic resection of DOACs was significantly lower than that of warfarin.4.As for the perioperative management strategies of anticoagulants,through traditional head-to-head meta-analysis and network meta-analysis,we found that warfarin with HB significantly increased the risk of PPB(Traditional Meta:OR=1.918;95%CI:0.132-3.250;P=0.016,I2=6.9%;Network Meta:OR=0.44,95%CI:0.15-0.86).There was no significant difference in PPB rates between DOACs and warfarin in cessation group,and continuation group.And the HB did not significantly increase the PPB rate for DOACs.Moreover,the cessation of warfarin unbridged strategy had the greatest likelihood of having the lowest PPB rate(61.75%)in a rank probability order.5.Through sensitivity analysis,we found that the above research results were stable,and the sources of heterogeneity were also found in all the studies with moderate heterogeneity.Meta-regression showed that confounding factors did not influence the results.In summary,this study objectively evaluated the literature based on evidencebased medicine methodology,and finally reached the following conclusions: 1.The incidence of total PPB in the DOACs group was significantly lower than that of warfarin,especially after ESD.There was no statistical difference in PPB risk between the two in other endoscopic resection methods,lesion sites and types of DOACs.2.With the accumulation of publication year and sample size,the incidence of PPB in DOACs was significantly lower than that of warfarin;3.For the perioperative management strategy of anticoagulants,HB can significantly increase the risk of warfarin PPB.The innovation of this study is that we analyzed anticoagulants and anticoagulant strategies for the PPB risk in the perioperative period of endoscopic resection from the perspective of evidence-based medicine for the first time.In addition,cumulative meta and other methodological methods were used to provide data support for clinical research from the perspective of evidence-based medicine.In addition,we also conducted traditional meta-analysis and network meta-analysis for different anticoagulant management strategies to increase the credibility of the evidence.In conclusion,this study provides high-quality evidence-based medicine evidence for clinical decision making and guideline setting,and the data have good clinical applicability.