This systematic review and meta-analysis has been registered in the International Prospective Register of Systematic Reviews(CRD42020156197), and the protocol was conceived according to the Preferred Peporting Items for Systematic Review and Meta-analysis Protocols (supplemental table 1). If there was any changes generated in relation to this protocol, PROSPERO registration information will be revised consequently.
Data sources and search strategy
We will follow the PRISMA (preferred reporting items for systematic reviews and meta-analyses) and the reporting MOOSE (Meta-analyses of Observational Studies in Epidemiology) when performing this study[17,18].
The following databases will be used to comprehensively search for relevant keywords: PubMed, Web of science, Cochrane Library and China national knowledge infrastructure(CNKI). The search will be performed for studies from inception to September 30, 2019 to locate all potentially eligible studies.
The search strategy will be conducted as follows: “Pradaxa” or “dabigatran”, “xareltro” or “rivaroxaban”. For the theme “atrial fibrillation”, we will use “atrial fibrillation” or “AF”. Study type will include real world studies, observational studies and registry studies. Additionally, the language of the publications will be limited to English and Chinese. As study population will be Asian, the main study site will not out of Asia, for instance mainland of China, Hongkong, Taiwan, Korea, Japan, Singapore and etc.
Studies will be choosen if they met the following criteria: Asian patients with NVAF; treatments with rivaroxaban and dabigatran; real world studies including prospective or respective cohort studies; Case control studies; registry studies.
Studies that include patients with mitral stenosis or prosthetic cardiac valves, mean or median follow-up duration<6 months, and study participants<200. For trials reporting multiple publications, the most relevant data will be extracted.
Two investigators(LJ and MZ) independently extracted the relevant information from each included study regarding the population, interventions, comparisons, the study design, patient characteristics, the number of enrolled patients, follow-up duration, and outcomes of interested. Outcome measures include safety and efficacy indicators. Safety indicators include intracranial hemorrhage, major bleeding and gastrointestinal bleeding. Efficacy indicators include systemic embolism and stroke.
The Newcastle Ottawa quality assessment scale (NOS) will be utilised to assess the risk of bias for all included studies. NOS is recommended by Cochrane Collaboration to evaluate the quality of literature in retrospective cohort studies, and it has eight items included in three domain, i.e.selection (representativeness), comparability(due to design or analysis), and outcomes(assessment and follow-up). Two investigators will review the selected articles separately and evaluate them. Disagreements will be settled by discussions between two investigators or consulting with a third expert in this field.
Incidence rate for primary and secondary outcomes will be accessed in this study. Primary outcomes will include stroke, systemic embolism and major bleeding, and secondary outcomes will contain ischemic stroke, gastrointestinal bleeding and intracranial hemorrhages. 95% confidence interval will be used for interval estimation, P value will be used to determine whether the combined effect size has statistical significance, and P value of < 0.05 represents a statistical significance. The statistical heterogeneity of the literature will be analyzed by I2 test. I2 of > 50% will indicate substantial heterogeneity among studies, a random-effects model will be used. Otherwise, we will use a fixed-effects model for evaluation.
Patient and Public Involvement
No patient involved
Publication bias assessment
The publication bias of the included studies will be considered if more than 10 studies will be included in the process of data processing. The possible methods may contain the funned plot, Egger’s intercept and Begg and Mazumdar’s text.