Systematic Review And Meta Analysis Of Stroke And Bleeding Risk Scores For Patients With Nonvalvular Atrial Fibrillation

Background:For the evaluation of efficacy and safety of anticoagulant drug of atrial fibrillation?AF?patients,several embolism and bleeding risk score systems have beenestablished,includingCHADS2,CHA2DS2-VASc,HAS-BLED,HEMORR₂HAGES,ATRIA and ORBIT.However,there are still controversies about the predictive value and accuracy of correlation scores for embolism or major bleeding events.Objective:We performed three systematic review and meta-analysis respectively to compare CHADS₂ and CHA₂DS₂-VASc scores in predicting the risk of stroke and thromboembolism in patients with nonvalvular atrial fibrillation?NVAF?,the diagnostic accuracy between HAS-BLED score and HEMORR₂HAGES,ATRIA,CHADS₂,CHA₂DS₂-VASc score,and the predictive ability by using HAS-BLED and ORBIT scores,and in order to provide a basis for the selection of criteria for the risk of embolism and bleeding in anticoagulated patients with atrial fibrillation.Methods:We systematically searched the Cochrane Library,Elsevier,PubMed,Embase databases and Chinese databases for relevant studies.Data extraction and analysis are based on predefined clinical outcomes.Statistical analysis was performed with Review Manager software.We chose the C-statistic to reflect the diagnostic value.There are other statistics,such as Z-statistic,net reclassification improvement?NRI?,integrated discrimination improvement?IDI?.Results:1.Comparison of CHADS₂ and CHA₂DS₂-VASc scores in predicting the risk of stroke and thromboembolism in patients with NVAF.A total of eleven studies were included.The result showed that when analyzed as a continuous variable,the C-statistics for the CHADS₂ and CHA₂DS₂-VASc scores were 0.660?0.650-0.717?and 0.697?0.637-0.724?.The pooled C-statistics for the CHADS₂ and CHA₂DS₂-VASc scores were 0.66?0.66-0.67?and 0.67?0.66-0.68?,respectively.When analyzed as a categorical variable,the C-statistics for the CHADS₂ and CHA₂DS₂-VASc scores were 0.630?0.586-0.722?and 0.606?0.521-0.850?.The pooled C-statistics for the CHADS₂ and CHA₂DS₂-VASc scores were0.65?0.62-0.67?and 0.63?0.59-0.68?,respectively.Because of the high heterogeneity across studies,the results should be interpreted cautiously.The average ratio of adverse event in the low-risk group of CHA₂DS₂-VASc was less than that of CHADS₂?0.54%vs 1.40%,P<0.05?.The average proportion of the high-risk group of CHA₂DS₂-VASc was greater than that of CHADS₂?81.0%vs 46.0%,P<0.05?.2.Comparison of HAS-BLED and HEMORR₂HAGES,ATRIA,CHADS_2,CHA₂DS₂-VASc sorces in predicting the risk of major bleeding in anticoagulated patients with NVAF.A total of eleven studies were identified.The results showed that the C-statistics for HAS-BLED,HEMORR₂HAGES and ATRIA scores were 0.66?0.60-0.69?,0.63?0.60-0.67?and0.61?0.59-0.69?.TheC-statisticsforCHADS₂ and CHA₂DS₂-VASc scores were 0.53?0.51-0.59?and 0.56?0.53-0.58?.The pooled C-statistic were 0.65?0.61-0.69?,0.63?0.61-0.66?,0.63?0.56-0.72?,0.55?0.49-0.61??0.56?0.53-0.59?,respectively.HAS-BLED vs HEMORR₂HAGES?Z=0.88,P>0.05?,HAS-BLED vs ATRIA?Z=0.49,P>0.05?,HAS-BLED vs CHADS₂?Z=2.72,P<0.01?,HAS-BLED vs CHA₂DS₂-VASc?Z=3.53,P<0.01?.The analysis of NRI and IDI demonstrates that the HAS-BLED score had better prediction accuracy for major bleeding risk than HEMORR₂HAGES or ATRIA bleeding scores,and CHADS₂ or CHA2DS2-VASc embolism scores.3.Comparison of ORBIT and HAS-BLED scores in predicting the risk of major bleeding in anticoagulated patients with NVAF.A total of seven studies were included.The results showed that the C-statistic of continuous variable of major bleeding was 0.65?0.60-0.69?for ORBIT score and0.63?0.60-0.66?for HAS-BLED score.Compared with HAS-BLED,more anticoagulated patients with atrial fibrillation?88.45%vs 32.59%?and major bleeding events?75.57%vs 25.57%?in the ORBIT score were categorized as low risk.The ORBIT score had 1.21,1.73 and 1.44-fold risk of major bleeding in the low,intermediate and high risk,respectively.The calibration analysis demonstrated that the ORBIT score under-predicted the risk of major bleeding.The odds ratio?OR?were0.64?0.37–1.10?,0.63?0.38–1.05?and 0.64?0.38–1.06?in the low,intermediate and high risk,respectively.Conclusion:1.The CHADS₂ and CHA₂DS₂-VASc scores have similar predictive value for stroke and TE risk in NVAF patients.2.The CHA₂DS₂-VASc score identifies truly"low risk"NVAF patients and classifies more patients into high risk,so as to direct anticoagulation more accurately.3.The accuracy of HAS-BLED score in predicting major bleeding in anticoagulated patients with NVAF was better than HEMORR₂HAGES,ATRIA bleeding scores,and CHADS₂,CHA₂DS₂-VASc embolism scores.4.The HAS-BLED score is currently the optimal choice for assess the risk of major bleeding in anticoagulated patients with NVAF in clinical practice.