The Effect Of Antithrombotic Regimens In Patients With Atrial Fibrillation Undergoing Coronary Artery Stenting

Part I Safety and Efficacy of different anticoagulant therapy regimen InAtrial Fibrillation Patients After Percutaneous Coronary InterventionAim To evaluate the short-term safety and efficacy of different anticoagulant therapy regimens in patients with atrial fibrillation after coronary artery stenting.Methods 246 atrial fibrillation patients undergoing coronary artery stenting in our hospital from January 2005 to December 2015 were involved and separated into three different anticoagulant therapy regimen groups: dual antiplatelet anticoagulant group(treated with aspirin and clopidogrel,DT group),triple anticoagulant group(treated with warfarin,aspirin and clopidogrel,TT group)and warfarin and single antiplatelet group(treated with warfarin and aspirin,or with warfarin and clopidogrel,WS group).We compared the clinical and laboratory parameters between three groups.Furthermore,we compared the 1-year risk of major bleeding and major adverse cardiac and cerebrovascular event(MACCE)between three groups.Result Among the 246 patients enrolled,there were 68 patients in the DT group,34 patients in the TT group and 139 patients in the WS group.There were 159 males and 187 females with the mean age was 67.3±5.4 year-old.After 1-year follow-up,the rate of major bleeding in three groups were: DD group 0%,TT group 18.2%,WS group 7.2%,which were significantly different between groups.Furthermore,10 patients died,50 cases had myocardial infarction,40 undergone coronary artery revascularization,26 with stroke,and 1 stent thrombosis.The rates of MACCE were: DD group 53.1%,TT group 45.4%,WS group 42.8%,which were similar between groups(P > 0.05).However,the rate of ischemic stroke was increased in patients treated with aspirin and clopidogrel.Conclusion For atrial fibrillation undergoing coronary artery stenting,triple anticoagulant treatment could significantly increase the risk of major bleeding with similar rates of MACCE.However,dual anticoagulants therapy was with the lower rate of major bleeding.Meanwhile,the rate of MACCE were comparable between groups.However,dual anticoagulant treatment with aspirin and clopidogrel could increased the rate of ischemic stroke.Part Ⅱ The effect of antithrombotic regimens in patients with atrialfibrillation undergoing coronary artery stenting:a meta-analysisAim By undertaking a meta-analysis of 31,346 patients from twenty-eight studies,we aimed to evaluate the efficacy and safety of triple versus dual antithrombotic regimen in patients taking oral anticoagulants undergoing coronary artery stenting.Method1.Database Searching: We searched four databases,including MEDLINE,EMBASE,the Cochrane Controlled Clinical Trials Register Database and Wan Fang Database,for the randomized clinical trials ans cohort studies about triple antithrombosis in patients with oral anticoagulation undergoing coronary artery stenting.2.Literature Screening: Based on the inclusion criterias and exclusion criterias,the Endnote Reference management software was used to edit all included literatures.After initial and secondary removale the unwanted papers,the randomized controlled trials and cohort studies meeting our criterias were included for further analysis.3.Data Collection: We used a sata extraction table,which includes basic patients and literature information,assessment of literature risk of bias of risk as well as primary and secondary clinical outcomes,for all data collection from included studies.Major clinical events were major adverse cardiac and cerebrovascular events.Secondary clinical events included all-cause mortality,cardiovascular death,myocardial infarction,stroke,stent thrombosis,major bleeding and adverse events.If the required data was unavailable,we tried to contact the corresponding author for the required information collection.4.Quality Assessment: We evaluated the quality of randomized clinical trials involved in our study by using the JADAD scale table,including random allocation sequence(adequate=2,unclear=1,unadequate=0),adequacy of allocation concealment((adequate=2,unclear=1,unadequate=0)),blinding(adequate=2,unclear=1,unadequate=0),and retraction(description=1,undescription=0).Overall scale 1-3 represented low quality,4-7 represented high quality.On the other hand,we used the Newcastle-Ottawa Scale to evaluate the quality of cohort studies,including participant selection,comparability,expose assessment and result evaluation.NOS used the half-quantization with star system to evaluate the quality of included studies.Nine stars means the highest quality.5.Data Analysis: We used the Stata 14.0 software for data analysis with random-effect model.Forest plot was used to show all clinical results.The heterogeneity was assessed and I2> 50% representing high level of heterogeneity.When significant heterogeneity occurring,the sensitivity analyses and subgroup analysis were carried out to exclude the large source of heterogeneity.Result1.Eight hundred and ninty-four articles were retrieved after searching literature databases,i.e.MEDLINE,EMBASE,the Cochrane Database and Wan Fang Database.A total of one hundred and sisty-five articles were included for further analysis after literature pruning to remove initial five hundred and twenty-nine articles and subsequent one hundred and thirty-seven articles.Finally,twenty-eight studies enrolling 31,346 patients with a mean follow-up of 14.2 months were included.2.There were no statistical significant differences between these two groups in terms of age,sex,hypertension,and atrial fibrillation prevalence.3.Only one study was randomized clinical trial,which was with high quality.In other twenty-seven cohort studies,thirteen of those was prospective design with high quality and 14 was retrospective design with low quality.4.Of twenty-five studies,there were 14,782 patients in the triple antithrombotic group,and 3,399 had adverse cardiac and cerebrovascular events(22.9%).There were 20,706 patients in the dual antithrombotic group,and 5,511 had adverse cardiac and cerebrovascular events(26.6%).Rates of major adverse cardiac and cerebrovascular events was similar between the triple and dual antithrombotic groups [RR,0.95,95% CI,(0.84,1.07),P = 0.39;I2 = 83.7%].Although there was a high level of heterogeneity,sensitivity analyses did not find the affected results by excluding each one of the studies.Among different antithrombotic regimens,the risk of adverse cardiac and cerebrovascular events was lowest in patients with triple antithrombotic therapy(oral anticoagulants,clopidogrel and aspirin),and highest in patients taking warfarin and aspirin dual antithrombotic regimen.5.Of twenty-five studies that reporting the data about mortalty,there were 14,782 patients in the triple antithrombotic group,and 1,416 died(9.5%).There were 20,706 patients in the dual antithrombotic group,and 2,722 died(13.1%).Rates of mortality was similar between the two groups [RR,0.94,95% CI,(0.78,1.12),P= 0.46;I2 = 76.9%].Both the Begg and Egger test did not find high level of reporting heterogeneity,and sensitivity analyses did not find the affected results by excluding each one of the studies.Among different antithrombotic regimens,the risk of mortality was low in patients with dual antithrombotic therapy(warfarin and clopidogrel).6.Of twenty-one studies that showing data about myocardial infarction,there were 8,154 patients in the triple antithrombotic group,and 448 had myocardial infarction(5.5%).There were 12,186 patients in the dual antithrombotic group,and 704 had myocardial infarction(5.8%).Rates of myocardial infarction was comparable between the two groups [RR,0.94,95% CI,(0.83,1.07),P= 0.35;I2 = 35.4%].Both the Begg and Egger test did not find high level of reporting heterogeneity,and sensitivity analyses did not find the affected results by excluding each one of the studies.Among different antithrombotic regimens,the risk of myocardial infarction was low in patients with dual antithrombotic therapy(warfarin and clopidogrel).7.Of ninteen studies that reporting the data about stroke,there were 12,769 patients in the triple antithrombotic group,and 423 had stroke(3.3%).There were 17,056 patients in the dual antithrombotic group,and 729 had stroke(4.3%).Rates of stroke was significantly lower in the the triple antithrombotic group [RR,0.80,95% CI,(0.70,0.90),P< 0.001;I2 = 45.9%].Both the Begg and Egger test did not find high level of reporting heterogeneity,and sensitivity analyses did not find the affected results by excluding each one of the studies.Among different antithrombotic regimens,the risk of stroke was low in patients with triple antithrombotic therapy(oral anticoagulants,clopidogrel and aspirin),or dual antithrombotic therapy(warfarin and clopidogrel).8.Of thirteen studies that reporting the data about stent thrombosis,there were 4,188 patients in the triple antithrombotic group,and 72 had stent thrombosis(1.7%).There were 7,779 patients in the dual antithrombotic group,and 145 had stent thrombosis(1.8%).Rates of stent thrombosis was similar between the two groups [RR,0.97,95% CI,(0.69,1.36),P=0.86;I2 = 14.6%].Both the Begg and Egger test did not find high level of reporting heterogeneity,and sensitivity analyses did not find the affected results by excluding each one of the studies.Among different antithrombotic regimens,the risk of stent thrombosis was low in patients with triple antithrombotic therapy(oral anticoagulants,clopidogrel and aspirin).9.Of ninteen studies that reporting the data about major bleeding,there were 14,831 patients in the triple antithrombotic group,and 1,742 had major bleeding(11.7%).There were 18,390 patients in the dual antithrombotic group,and 1,259 had major bleeding(6.8%).Rates of major bleeding was significantly higher in the the triple antithrombotic group [RR,1.71,95% CI,(1.41,2.06),P< 0.001;I2 = 69.9%].Both the Begg and Egger test did not find high level of reporting heterogeneity,and sensitivity analyses did not find the affected results by excluding each one of the studies.Among different antithrombotic regimens,the risk of bleeding was low in patients with dual antithrombotic therapy(warfarin and clopidogrel).10.Adverse events included mortalyt,myocardial infarction,stent thrombosis,stroke and major bleeding.Of twenty-four studies that reporting the data,there were 14,627 patients in the triple antithrombotic group,and 5,136 had events(35.1%).There were 18,186 patients in the dual antithrombotic group,and 6,533 had events(35.9%).Triple antithrombotic therapy was associated with a trend of increased risk of adverse events [RR,1.07,95% CI,(0.97,1.17),P= 0.18;I2 = 82.9%].Both the Begg and Egger test did not find high level of reporting heterogeneity,and sensitivity analyses did not find the affected results by excluding each one of the studies.Among different antithrombotic regimens,the risk of adverse events was low in patients with dual antithrombotic therapy(warfarin and clopidogrel).11.Subgroup analysis was done to explore the effect of follow-up period in adverse cardiac and cerebrovascular events.Studies were devided into two groups,short-term follow-up(<12 months)and mediate-to-long follow-up(≥12 months).There were six studies with short-term follow-up and twenty-two studies with mediate-to-long follow-up.In studies with short-term follow,triple antithrombotic therapy was associated with a trend of decreased risk of adverse cardiac and cerebrovascular events [RR,0.76,95% CI,(0.55,1.05),P= 0.10;I2 = 31.9%].In studies with mediate-to-long follow,risk of adverse cardiac and cerebrovascular events was similar between the triple and dual antithrombotic groups [RR,0.98,95% CI,(0.85,1.12),P= 0.72;I2 = 86.2%].Conclusion1.For patients taking oral anticoagulants undergoing coronary artery stenting,triple antithrombotic therapy could reduce the risk of adverse cardiac and cerebrovascular event in short-term follow-up(<12 months);dual antithrombotic therapy with warfarin and clopidogrel could reduce the risk of adverse cardiac and cerebrovascular event in mediate-to-long follow-up(≥12 months).2.Triple antithrombotic therapy was associated with high risk of major bleeding.New oral anticoagulants and left atrial appendage closure could decrease the rate of bleeding.More randomized clinical trials are needed to confirm our findings.