The management of anticoagulants in patients with atrial fibrillation and history of falls or risk of falls: protocol for a systematic review and meta-analysis.

Background: Atrial fibrillation affects an estimated 33 million individuals worldwide and is a major cause of stroke, heart failure, and death. Anticoagulants substantially reduce the risk of stroke but are also associated with an increased risk of bleeding and especially intracranial hemorrhage which is the most concerning complication. Because of this, many patients are not offered anticoagulants, particularly patients at risk of falls or with a history of falls. It is unclear what anticoagulant treatment these patients should be offered. The Liverpool AF-Falls project aims to investigate this area, and this protocol for a systematic review and meta-analysis aims to define what is the most appropriate anticoagulant treatment option for the management of atrial fibrillation patients at risk of falls or with a history of falls.

Methods: This systematic review and meta-analysis will include randomized and non-randomized studies evaluating the safety and efficacy of different anticoagulant treatments (vitamin K antagonist and non-vitamin K antagonist oral anti-coagulant). Bibliographic databases (Cochrane Central Register of Controlled Trials, CINAHL, ClinicalTrials.gov , Embase, MEDLINE, Scopus and Web of Science) will be searched according to a pre-specified search strategy. Titles, abstracts, and full texts will be assessed by two independent reviewers and disagreements resolved with a third independent reviewer. The Cochrane Risk of Bias tool 2 (RoB 2) will be used to assess the risk of bias in randomized trials, and the Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) tool will be used for non-randomized studies. A pairwise meta-analysis based on the fixed and random-effects models will be conducted. Publication bias will be evaluated with a funnel plot and Egger's test. Heterogeneity will be assessed with the I statistic. If conditions for indirect comparison are met and sufficient data are available, a network meta-analysis will be conducted using frequentist and Bayesian methodologies.

Discussion: This review will be the first to summarize direct and indirect evidence on the safety and efficacy of anticoagulant treatments in atrial fibrillation patients at risk of falls or with a history of falls. The findings will be important to patients, clinicians, and health policy-makers to inform best practices in the use of these treatments.

Systematic Review Registration: PROSPERO registry number: CRD42020201086.