Comparison of effectiveness and safety of direct oral anticoagulants versus vitamin-k antagonists in elderly patients with atrial fibrillation: a systematic review and cost-effectiveness analysis protocol

BACKGROUND: Current evidence regarding the effectiveness and safety of direct oral anticoagulants (DOACs) in the elderly with atrial fibrillation (AF) remains scarce. Based on the emerging evidence from real-world studies (RWSs) associated with DOACs, we will perform a systematic review and meta-analysis of data from RWSs and randomized controlled trials (RCTs) to compare the effectiveness, safety and cost of DOACs versus Vitamin K antagonists (VKAs) in elderly patients with AF. METHODS: The MEDLINE, EMBASE and Cochrane Library databases will be systematically searched until June 30, 2019 for eligible RWSs and RCTs that reported the clinical outcomes between DOACs and VKAs in elderly patients with AF. The effectiveness outcome is stroke or systemic embolism (SE), and the safety outcomes are major bleeding, intracranial haemorrhage (ICH), gastrointestinal bleeding (GIB), myocardial infarction (MI) and all-cause mortality. A random-effects model will be used to calculate adjusted hazard ratios (HRs) for RWSs and relative risks (RRs) for RCTs, separately. The interaction analysis and the ratio of HRs (RHRs) will be applied to compare the treatment effect difference between RWSs and RCTs. A Markov model will be constructed to evaluate the cost-effectiveness of DOACs versus VKAs in elderly AF patients in real-world setting. DISCUSSION: This study will summarize all available evidences from RWSs and RCTs for a comprehensive and rigorous systematic review on the effectiveness and safety associated with DOACs, as well as perform a cost-effectiveness analysis to evaluate the price performance of DOACs among elderly AF patients in real clinical setting. TRIAL REGISTRATION: PROSPERO register platform (CRD42019142881, www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID =142881).