Abstract
BACKGROUND: Several observational studies have shown that the inappropriate dosing use of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) that does not conform to recommendations is becoming a widespread phenomenon. Therefore, we performed a meta-analysis and systematic review to assess the effect of non-recommended doses versus recommended doses of DOACs on the effectiveness and safety outcomes among AF patients. METHODS: The PubMed and Ovid databases were systematically searched to identify the relevant studies until December 2020. The effect estimates were hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled using a fixed-effects model (I(2) ≤ 50%) or a random-effects model (I(2) > 50%). RESULTS: A total of 11 studies were included in this meta-analysis. Compared with recommended dosing of DOACs, non-recommended low dosing of DOACs was associated with increased risks of stroke or systemic embolism (SSE, HR = 1.29, 95% CI 1.12-1.49) and all-cause death (HR = 1.37, 95% CI 1.15-1.62), but not the ischemic stroke, myocardial infarction, gastrointestinal bleeding, intracranial bleeding, and major bleeding. Compared with recommended dosing of DOACs, non-recommended high dosing of DOACs was associated with increased risks of SSE (HR = 1.44, 95% CI 1.01-2.04), major bleeding (HR = 1.99, 95% CI 1.48-2.68), and all-cause death(HR = 1.38, 95% CI 1.02-1.87). CONCLUSION: Compared with recommended dosing of DOACs, non-recommended low dosing of DOACs was associated with increased risks of SSE and all-cause death. Further study should confirm the findings of non-recommended high dosing versus recommended dosing of DOACs.