Therefore, our study was close to the real-world circumstances. in all kinds of NOACs than VKAs in the Asian AF patients (HR: 0.633; 95% confidence interval: 0.535C0.748; 0.001). Additionally, the GIB risks of different NOACs were apixaban (HR: 0.392), edoxaban (HR: 0.603), dabigatran (HR: 0.685), and rivaroxaban (HR: 0.794), respectively. NOACs significantly reduced the risk of GIB in the Asian AF patients compared with VKAs. In the four NOACs compared with VKAs, apixaban probably had a trend of the least GIB risk. We need further head-to-head studies of different NOACs to confirm which NOAC is the most suitable for Asian AF patients and to know the optimal dosage regimen of different NOACs. less than 0.10. 2.4. GRADE System, Meta-Regressions, and Sensitivity Analyses The GRADE system was used to grade the quality of evidence [17]. The GRADE system judged evidence of having a lower quality if there were study limitations, inconsistency, indirectness, imprecision, or publication bias. Large effect, dose-response, or plausible confounders were factors that caused higher quality. We made meta-regressions BIMP3 to examine the important and common covariates which might influence the outcomes. We also performed sensitivity analyses by excluding one study at a time and calculating the pooled HRs. 3. Results 3.1. Study Search and Research Evaluation We retrieved 1213 records identified through database searching and no additional records identified through other sources. Eighty-four duplicated records were removed. One thousand and twenty-eight incompatible titles, case reports, or abstracts were excluded. One hundred and one full-text articles assessed for eligibility were included (Figure 1). Then sixty-four articles without GIB data or using inappropriate statistical methods were ruled out. Fifteen articles probably extracted from the identical database or the same population were not applied [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32]. Sixteen articles investigating non-Asians or not fully Asians were not enrolled [33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48]. Open in a separate window Figure 1 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart. Preferred reporting items for systematic reviews and meta-analyses flow diagram for the searching and identification of included studies. Finally, six articles were included for meticulous evaluation after eliminating the references violating the inclusion criteria. First author, published year, type of interventions, study design, number of patients, average age, data source, country, and outcome are listed in Table 1. This meta-analysis included two RCTs [49,50], which were appraised by ROB 2.0 (Figure 2a). The other four retrospective studies were enrolled [51,52,53,54] and were evaluated by ROBINS-I (Figure 2b). Open in a separate window Figure 2 (a) Summary of each randomized controlled trial (RCT) appraised by ROB 2.0. (b) Summary of each retrospective study evaluated by ROBINS-I. Table 1 Summary of the retrieved articles for PF-4800567 gastrointestinal bleeding risk of non-vitamin K antagonist oral anticoagulants and vitamin K antagonists in the Asian atrial fibrillation patients. 0.001; I2: 61.6%) PF-4800567 (Figure 3a). The retrospective subgroup also showed a significantly lower GIB risk of NOACs than VKAs (HR: 0.610; 95% CI, 0.509 to 0.730; 0.001; I2: 68.9%). However, the RCT subgroup revealed a trend toward less GIB risk for NOAC users but did not show statistical significance (HR: 0.864; 95% CI, 0.529 to 1 1.409; = 0.557; I2: 0%) (Figure 3b). Open in a separate window Figure PF-4800567 3 (a) Forrest plot of comparison: all novel oral anticoagulants versus vitamin K antagonists. (b) Forrest plot of comparison: the retrospective studies subgroup and the RCTs subgroup. Table 2 Meta-analyses of gastrointestinal bleeding in different groups. = 0.025; I2: 82.0%) (Figure 4a), edoxaban (HR: 0.603; 95% CI, 0.434 to 0.839; = 0.003; I2: 35.0%) (Figure 4b), dabigatran (HR: 0.685; 95%.