Direct oral anticoagulant- vs vitamin K antagonist-related nontraumatic intracerebral hemorrhage

Objective: To compare the neuroimaging profile and clinical outcomes among patients with intracerebral hemorrhage (ICH) related to use of vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF). Methods: We evaluated consecutive patients with NVAF with nontraumatic, anticoagulantrelated ICH admitted at 13 tertiary stroke care centers over a 12-month period. We also performed a systematic review and meta-analysis of eligible observational studies reporting baseline characteristics and outcomes among patients with VKA-or DOAC-related ICH. Results: We prospectively evaluated 161 patients with anticoagulation-related ICH (mean age 75.6 +/- 9.8 years, 57.8% men, median admission NIH Stroke Scale [NIHSSadm] score 13 points, interquartile range 6-21). DOAC-related (n = 47) and VKA-related (n = 114) ICH did not differ in demographics, vascular risk factors, HAS-BLED and CHA(2)DS(2)-VASc scores, and antiplatelet pretreatment except for a higher prevalence of chronic kidney disease in VKA-related ICH. Patients with DOAC-related ICH had lower median NIHSSadm scores (8 [3-14] vs 15 [7-25] points, p = 0.003), median baseline hematoma volume (12.8 [4-40] vs 24.3 [11-58.8] cm(3), p = 0.007), and median ICH score (1 [0-2] vs 2 [1-3] points, p = 0.049). Severe ICH (> 2 points) was less prevalent in DOAC-related ICH (17.0% vs 36.8%, p = 0.013). In multivariable analyses, DOAC-related ICH was independently associated with lower baseline hematoma volume (p = 0.006), lower NIHSSadm scores (p = 0.022), and lower likelihood of severe ICH (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.13-0.87, p = 0.025). In meta-analysis of eligible studies, DOAC-related ICH was associated with lower baseline hematoma volumes on admission CT (standardized mean difference 5 20.57, 95% CI 21.02 to 20.12, p = 0.010) and lower in-hospital mortality rates (OR = 0.44, 95% CI 0.21-0.91, p = 0.030). Conclusions: DOAC-related ICH is associated with smaller baseline hematoma volume and lesser neurologic deficit at hospital admission compared to VKA-related ICH.