Impact of Oral Anticoagulation and Adenosine Diphosphate Inhibitor Therapies on Short-term Outcome of Traumatic Brain Injury.

Abstract

Usage of oral anticoagulants (OACs) or adenosine diphosphate inhibitors (ADPi) is known to increase the risk of bleeding. We aimed to investigate the impact of OAC and ADPi therapies on short-term outcomes after traumatic brain injury (TBI). All adult patients hospitalized for TBI in Finland during 2005-2018 were retrospectively studied using a combination of national registries. Usage of pharmacy-purchased OACs and ADPi at the time of TBI was analyzed with the pill-counting method (Social Insurance Institution of Finland). The primary outcome was 30-day case-fatality (Finnish Cause of Death Registry). The secondary outcomes were acute neurosurgical operation (ANO) and admission duration (Finnish Care Register for Health Care). Baseline characteristics were adjusted with multivariable regression, including age, sex, comorbidities, skull or facial fracture, OAC/ADPi treatment, initial admission location, and the year of TBI admission. The study population included 57,056 persons (mean age 66 years) of whom 0.9% used direct OACs (DOACs), 7.1% vitamin K antagonists (VKA), and 2.3% ADPi. Patients with VKAs had higher case-fatality than patients without OAC (15.4% vs 7.1%; adjusted hazard ratio [aHR] 1.35, CI 1.23-1.48; p < 0.0001). Case-fatality was lower with DOACs (8.4%) than with VKAs (aHR 0.62, CI 0.44-0.87; p = 0.005) and was not different from patients without OACs (aHR 0.93, CI 0.69-1.26; p = 0.634). VKA usage was associated with a higher neurosurgical operation rate compared with non-OAC patients (9.1% vs 8.3%; adjusted odds ratio 1.33, CI 1.17-1.52; p < 0.0001). There was no difference in operation rate between DOAC and VKA. ADPi was not associated with case-fatality or operation rate in the adjusted analyses. VKAs and DOACs were not associated with longer admission length compared with the non-OAC group, whereas the admissions were longer in the ADPi group compared with the non-ADPi group. Preinjury use of VKA is associated with increases in short-term mortality and in need for ANOs after TBI. DOACs are associated with lower fatality than VKAs after TBI. ADPi were not independently associated with the outcomes studied. These results point to relative safety of DOACs or ADPi in patients at risk of head trauma and encourage to choose DOACs when oral anticoagulation is required. This study provides Class II evidence that among adults with TBI, mortality was significantly increased in those using VKAs but not in those using DOACs or ADPi.