<p>Japanese patients with atrial fibrillation (AF) often receive underdosed direct oral anticoagulants (DOACs), deviating from standard guidelines. The impact of underdosing compared to standard dosing on thromboembolic and bleeding risks in this population remains unclear. This meta-analysis included 13 studies with 37,633 Japanese AF patients comparing underdose and standard dose groups. Efficacy outcomes included stroke or systemic embolism and ischemic stroke. Safety outcomes were major bleeding, intracranial hemorrhage, gastrointestinal bleeding, all bleeding, and all-cause mortality. Hazard ratios and 95% confidence intervals were pooled using a random-effects model. Sensitivity analyses evaluated robustness by including studies with confounder controls. Underdosing showed similar risks of stroke or systemic embolism (HR 1.03, 95% CI 0.87–1.22) and ischemic stroke (HR 1.05, 95% CI 0.85–1.31) compared to standard dosing. Major bleeding (HR 0.86; 95% CI 0.72–1.04) and all bleeding (HR 0.80; 95% CI 0.63–1.03) showed a non-significant reduction with underdosing. Sensitivity analyses confirmed a significant&#xa0;reduction in major bleeding risk with underdosing (HR 0.77, 95% CI 0.64–0.94). All-cause mortality was significantly higher in the underdose group throughout the primary (HR 1.47, 95% CI 1.13–1.90) and sensitivity analyses. In conclusion,&#xa0;Japanese patients receiving an underdose of DOACs had thromboembolic event rates comparable to those seen with standard dosing, with a reduction in bleeding events confirmed by sensitivity analyses and higher mortality. These findings indicate that ethnic-specific factors may influence DOAC effects, warranting further investigation to validate these observations and inform tailored dosing recommendations for Japanese AF patients.</p> Graphical Abstract <p>Summary of clinical outcomes from a meta-analysis of 13 studies involving 37,633 patients with atrial fibrillation receiving off-label underdosed or standard-dose direct oral anticoagulants (DOACs). The left and right panels present hazard ratios and 95% confidence intervals for ischemic stroke, major bleeding, and all-cause mortality from the primary and sensitivity analyses, respectively. At the bottom, a “Central Message” panel visually highlights the study’s main findings: ischemic stroke incidence was comparable between groups; major bleeding was significantly reduced in the underdose group in sensitivity analysis; and all-cause mortality was consistently higher with underdosing. AF = atrial fibrillation; DOAC = direct oral anticoagulant; RCT = randomized controlled trial</p>