From the Neurocenter (J.P.P.), Department of Neurosurgery and Turku Brain Injury Center; Neurocenter (J.O.R.), Department of Neurology, Turku University Hospital and University of Turku; Clinical Neurosciences (J.O.T.S.), University of Turku; Department of Neurology (J.O.T.S.), North Karelia Central Hospital, Siun sote, Joensuu; Department of Neurosurgery (T.M.L.), Tampere University Hospital and Tampere University; Clinical Research Center (P.R.), Turku University Hospital and University of Turku; Heart Centre and Center for Population Health Research (V.K.), Turku University Hospital and University of Turku; Research Center of Applied and Preventive Cardiovascular Medicine (V.K.), University of Turku; Administrative Center (V.K.), Hospital District of Southwest Finland, Turku; and Department of Public Health (V.K.), Faculty of Medicine, University of Helsinki, Finland.
Neurology. 2022 Sep 13;99(11):e1122-e1130. doi: 10.1212/WNL.0000000000200834. Epub 2022 Jun 28.
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; < 0.0001). Case-fatality was lower with DOACs (8.4%) than with VKAs (aHR 0.62, CI 0.44-0.87; = 0.005) and was not different from patients without OACs (aHR 0.93, CI 0.69-1.26; = 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; < 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.
使用口服抗凝剂(OACs)或腺苷二磷酸抑制剂(ADPi)已知会增加出血风险。我们旨在研究 OAC 和 ADPi 治疗对创伤性脑损伤(TBI)后短期结局的影响。
使用国家登记处的组合,回顾性研究了芬兰 2005 年至 2018 年期间因 TBI 住院的所有成年患者。使用药房购买的 OAC 和 ADPi 在 TBI 时的使用情况通过药片计数法(芬兰社会保险机构)进行分析。主要结局为 30 天病死率(芬兰死因登记处)。次要结局为急性神经外科手术(ANO)和入院时间(芬兰医疗保健登记处)。使用多变量回归调整了基线特征,包括年龄、性别、合并症、颅骨或面部骨折、OAC/ADPi 治疗、初始入院地点和 TBI 入院年份。
研究人群包括 57056 人(平均年龄 66 岁),其中 0.9%使用直接 OAC(DOACs),7.1%使用维生素 K 拮抗剂(VKA),2.3%使用 ADPi。使用 VKA 的患者病死率高于未使用 OAC 的患者(15.4%比 7.1%;调整后的危险比[aHR]1.35,CI1.23-1.48;<0.0001)。与 VKA 相比,DOACs 的病死率更低(8.4%;aHR0.62,CI0.44-0.87;=0.005),与未使用 OAC 的患者无差异(aHR0.93,CI0.69-1.26;=0.634)。与非 OAC 患者相比,VKA 使用率与更高的神经外科手术率相关(9.1%比 8.3%;调整后的优势比 1.33,CI1.17-1.52;<0.0001)。DOAC 与 VKA 之间的手术率无差异。在调整分析中,ADPi 与病死率或手术率无关。与非 OAC 组相比,VKA 和 DOAC 与入院时间延长无关,而与非 ADPi 组相比,ADPi 组的入院时间更长。
创伤前使用 VKA 与 TBI 后短期死亡率增加和需要 ANO 相关。与 VKA 相比,DOACs 与 TBI 后的病死率降低相关。ADPi 与研究结果无独立相关性。这些结果表明 DOACs 或 ADPi 在有头部创伤风险的患者中相对安全,并鼓励在需要口服抗凝治疗时选择 DOACs。
本研究提供了 II 级证据,表明在患有 TBI 的成年人中,使用 VKA 的患者死亡率显著增加,但使用 DOACs 或 ADPi 的患者死亡率没有增加。