Safety And Efficacy Of 10mg Rivaroxaban For Non-Valvular Atrial Fibrillation:A Meta-Analysis

BackgroundAtrial fibrillation is one of the most common types of arrhythmia.It is estimated that AF patients have a 4-to-5 fold increased risk of ischemic stroke(IS)compared to those without atrial fibrillation.Prevention of thromboembolism caused by atrial fibrillation is really essential.Rivaroxaban,a non-vitamin K antagonist oral anticoagulant,which functions by selectively blocking Xa factor in coagulation cascade,has been approved for treatment of non-valvular atrial fibrillation(NVAF)for a long time.Although 10mg rivaroxaban focused on anticoagulation in NVAF patients is only approved by Japan and Taiwan,China,and is limited in patients whose Creatine clearance(CrCl)are 30-49ml/min,it is still widely used around Asia in real-world clinical practice.PurposeWe performed this systematic review to analyze the safety and efficacy of treatment with 10mg rivaroxaban in patients with NVAF.MethodsWe searched PubMed,Embase and Cochrane Library until April 14,2020.and We also employed a backward snowballing method to review references from identified articles in above databases.All articles were searched by two independent authors.Participant in each included study who had been diagnosed with NVAF previously were divided into two groups according to whether they used 10mg rivaroxaban for anticoagulation or not.Assessment outcomes included three main categories:efficacy outcomes,safety outcomes and all-cause mortality.Efficacy outcomes included combination of IS and non-central nervous system systemic embolism(non-CNS SE),IS,non-CNS SE,composite efficacy,and myocardial infarction.Safety outcomes included intracranial hemorrhage,major bleeding,and gastrointestinal bleeding.We performed a meta-analysis to estimate pooled hazard ratios(HR)with 95%confidence interval(CI).I2 value was recognized as heterogeneity between studies.Fixed-effects model or random-effects model were used based on I2 value.We used the Grading of Recommendation,Assessment,Development and Evaluation(GRADE)criteria to grade the quality of pooled evidence for each outcome.Results1.A total of 8 observational studies were identified and included in this study and no randomized controlled trials were included.There were 51248 objects included in this study,20691 from 10mg rivaroxaban group and 30557 from control group,all of which were from Japan or Taiwan,China.2.For efficacy outcomes,our study showed that 10mg rivaroxaban was associated with increased risk of non-CNS SE(HR 2.82,95%CI 1.48-5.37,p=0.002),and myocardial infarction(HR 1.47,95%CI 1.11-1.94,p=0.007).There was no significant difference between two groups in terms of the combination of IS and non-CNS SE(HR 1.09,95%CI 0.81-1.46,p=0.557),IS(HR 1.28,95%CI 0.75-2.19,p=0.372)and composite efficacy(HR 1.05,95%CI 0.76-1.46,p=0.768).3.For safety outcomes,we found that 10mg rivaroxaban appeared to decrease the risk of gastrointestinal bleeding(HR 0.77,95%CI 0.59-1.00,p=0.050).There was no significant difference in terms of intracranial hemorrhage(HR 1.03,95%CI 0.85-1.24,p=0.789)and major bleeding(HR 0.95,95%CI 0.74-1.21,p=0.661).4.There was also no significant difference in all-cause mortality(HR 0.77,95%CI 0.59-1.00,p=0.050).5.Sub-group analysis showed that there were no differences between off-label 10mg rivaroxaban and standard-dose rivaroxaban in terms of the combination of IS and non-CNS SE(HR 1.47,95%CI 0.82-2.66,p=0.199),IS(HR 1.78,95%CI 0.76-4.19,p=0.184),composite efficacy(HR 1.26,95%CI 0.98-1.62,p=0.067),intracranial hemorrhage(HR 0.90,95%CI 0.48-1.68,p=0.737)and major bleeding(HR 0.94,95%CI 0.75-1.18,p=0.371).Conclusion1.Anticoagulation with 10mg rivaroxaban for NVAF is not associated with increased risk of the combination of IS and non-CNS SE,IS,composite efficacy,intracranial hemorrhage,major bleeding and all-cause mortality compared with standard-dose rivaroxaban.2.Anticoagulation with 10mg rivaroxaban for NVAF is associated with increased risk of non-CNS SE and myocardial infarction compared with standard-dose rivaroxaban.3.Anticoagulation with 10mg rivaroxaban for NVAF is associated with decreased risk of gastrointestinal bleeding in comparison with standard-dose rivaroxaban.4.Anticoagulation with off-label 10mg rivaroxaban for NVAF is not associated with increased risk of the combination of IS and non-CNS SE,IS,composite efficacy,intracranial hemorrhage and major bleeding compared with standard-dose rivaroxaban.