Volume and functional outcome of intracerebral hemorrhage according to oral anticoagulant type

Abstract

Objective: To compare intracerebral hemorrhage (ICH) volume and clinical outcome of non-vitamin K oral anticoagulants (NOAC)-associated ICH to warfarin-associated ICH.Methods: In this multicenter cross-sectional observational study of patients with anticoagulantassociated ICH, consecutive patients with NOAC-ICH were compared to those with warfarin-ICH selected from a population of 344 patients with anticoagulant-associated ICH. ICH volume was measured by an observer blinded to clinical details. Outcome measures were ICH volume and clinical outcome adjusted for confounding factors. Results:We compared 11 patients with NOAC-ICH to 52 patients with warfarin-ICH. The median ICH volume was 2.4 mL (interquartile range [IQR] 0.3-5.4 mL) for NOAC-ICH vs 8.9 mL (IQR 4.0-21.3 mL) for warfarin-ICH (p 5 0.0028). In univariate linear regression, use of warfarin (difference in cube root volume 1.61; 95% confidence interval [CI] 0.69 to 2.53) and lobar ICH location (compared with nonlobar ICH; difference in cube root volume 1.52; 95% CI 2.20 to 0.85) were associated with larger ICH volumes. In multivariable linear regression adjusting for confounding factors (sex, hypertension, previous ischemic stroke, white matter disease burden, and premorbid modified Rankin Scale score [mRS]), warfarin use remained independently associated with larger ICH (cube root) volumes (coefficient 0.64; 95% CI 0.24 to 1.25; p 5 0.042). Ordered logistic regression showed an increased odds of a worse clinical outcome (as measured by discharge mRS) in warfarin-ICH compared with NOAC-ICH: odds ratio 4.46 (95% CI 1.10 to 18.14; p 5 0.037). Conclusions:In this small prospective observational study, patients with NOAC-associated ICH had smaller ICH volumes and better clinical outcomes compared with warfarin-associated ICH. Intracerebral hemorrhage (ICH) is the most feared complication of oral anticoagulation, with an in-hospital mortality of 42%.1 Despite advances in ICH prevention, the global incidence of ICH has not declined, 2 likely secondary to the increase in anticoagulant-related ICH in the elderly. 3-5In large phase 3 randomized trials, patients in atrial fibrillation had half the incidence of ICH when taking non-vitamin K oral anticoagulants (NOACs) compared to warfarin, with similar efficacy in preventing ischemic stroke.6 Data on NOAC-associated ICH (NOAC-ICH) outside randomized trials are limited, and there is widespread concern that, without any currently available specific antidotes, those who have ICH while on NOACs might have larger ICH volumes and worse clinical outcomes than patients with warfarin-associated ICH (warfarin-ICH). 7,8 Although experimental models show that dabigatran 9 and rivaroxaban 10 -unlike warfarindo not increase ICH volume unless given at supratherapeutic doses, few data are available on the clinical and radiologic characteristics of NOAC-ICH. A small study from Japan recently

Acute subdural hematoma in patients on oral anticoagulant therapy: management and outcome

“…Because of their specific factor inhibition, DOACs do not influence the initial factor VII/VIIa interaction with TF, allowing for faster coagulation and reduced hematoma expansion. 33 Indeed, several experimental and clinical studies have reported on the benefit of DOACs in ICH. 3,7,24,29,33 However, no such benefit was observed in patients with aSDH in our study, and preinjury DOAC therapy was even associated with an increased midline shift.…”

“…33 Indeed, several experimental and clinical studies have reported on the benefit of DOACs in ICH. 3,7,24,29,33 However, no such benefit was observed in patients with aSDH in our study, and preinjury DOAC therapy was even associated with an increased midline shift. Fleck et al reported that the concentrations of TF depended on the location from which the tissue was obtained.…”

Serum Magnesium Levels and Outcomes in Patients With Acute Spontaneous Intracerebral Hemorrhage

“…Simple and multiple linear regression analyses were used to evaluate the associations between baseline characteristics and hematoma volume, square root of NIHSS score, and ICH score. Before simple and multiple linear regression analyses, admission hematoma volume was cube root transformed for each patient to satisfy statistical assumptions about normality of distribution 20. Similarly, admission NIHSS scores were square transformed for each patient to satisfy statistical assumptions about normality of distribution 21.…”

Intracranial Hemorrhage in Deep Vein Thrombosis/Pulmonary Embolus Patients Without Atrial Fibrillation

“…11,[13][14][15][36][37][38] When ICH does occur, the hemorrhages tends to be smaller, less severe, and less frequently fatal in patients on DOACs compared with patients on warfarin. [39][40][41] However, >600 000 patients per year in the United States require prolonged anticoagulation therapy for VTE. [17][18][19] With regard to ICH, a pooled analysis of RE-COVER/RE-COVER II revealed 0.1% rate of ICH in dabigatran group versus 0.2% in the warfarin group (P value not reported).…”