Abstract WP448: Safety of Heparin for Prophylaxis of Venous Thromboembolism in Oral Anticoagulation-Associated Intracerebral Hemorrhage

Abstract

Introduction: Patients with intracerebral hemorrhage (ICH) have a high risk of venous thromboembolism (VTE). Next to intermittent pneumatic compressions low-dose subcutaneous heparins represent the most intuitive treatment for VTE prophylaxis. However, in the specific setting of ICH their safety remains to be verified as randomized controlled trials are missing. The present study pooled individual data of patients with spontaneous primary ICH and OAC-ICH to explore the incidence of hemorrhagic complications during hospital stay among subgroups treated with heparins for VTE prophylaxis. Methods: We integrated both parts of the RETRACE-program (part-1: 2006-2010; part-2:2011-2015) and the single-center UKER-ICH registry (2006-2015). Including all patients receiving low-dose subcutaneous heparin for VTE prevention we pooled individual patient data of 1702 vitamin-K antagonist-(VKA) or non-VKA oral anticoagulants(NOAC)-related ICH patients treated at 22 tertiary-care centers across Germany and of 1022 primary spontaneous ICH patients from UKER. We defined intracranial hemorrhagic complications (IHC) during hospital stay as primary safety outcome measure. Secondary outcomes included mortality and functional outcome (modified Rankin Scale, mRS) at 3 months of patients with and without IHC. Results: IHC occurred in 1.7%(42/2416) of ICH patients. There were no differences in crude incidence rates among patients with VKA-ICH, NOAC-ICH and non-OAC-ICH (Log rank p=0.645; Breslow p=0.753; VKA-ICH: 27/1406[1.9%], NOAC-ICH 1/130[0.8%], non-OAC-ICH 14/880[1.6%];p=0.577). Detailed analysis according to days spent on heparin prophylaxis revealed no differences in rates of IHC per 1000 patient days (VKA-ICH: 1.49[1.00-2.14], NOAC-ICH 0.63[0.03-3.13], non-OAC-ICH 1.45[0.82-2.37]; p=0.687). Secondary outcomes showed differences in functional outcome (mRS=4-6: IHC: 29/37[78.4%] vs no-IHC: 1213/2048[59.2%];p=0.019) and mortality (IHC: 14/37[37.8%] vs no-IHC: 485/2048[23.7%];p=0.045) in disfavor of IHC-patients. Conclusions: Heparin administration for VTE prophylaxis in ICH patients appears to be safe without differently increased risks of IHC among non-OAC-ICH, VKA-ICH and NOAC-ICH.