Huttner Hagen B, Scherg Felix, Kopke Katarina, Schultze Michael, Kossack Nils, Gerner Stefan T, Kuramatsu Joji B, Schwab Stefan
Department of Neurology, University Hospital Giessen, Giessen, Germany.
BioPharmaceuticals Medical, AstraZeneca, Hamburg, Germany.
Neurol Res Pract. 2025 Mar 31;7(1):21. doi: 10.1186/s42466-025-00366-3.
Intracranial haemorrhage (ICH) is one of the most serious complications of anticoagulant therapy with oral factor Xa inhibitors (FXai). To meet an urgent medical need of optimising treatment pathways, we assessed the frequency of ICH during oral FXai treatment, as well as the associated burden on the German healthcare system.
Our study was based on a claims database comprising over 4 million people with statutory health insurance in Germany. The study included people initiating oral FXai treatment for the first time between 2016 and 2021, and who experienced ICH during a three-year treatment period. For a balanced comparison of hospitalisations, costs, and mortality, propensity score matching between patients with and without ICH was performed.
During the study period, 78,086 patients had started oral FXai therapy, of which 530 experienced ICH during the therapy. The incidence rate of ICH was highest within the first 90 days after the start of oral FXai therapy during follow-up with 0.64 events per 100 patient-years (PY; 95% CI: 0.52-0.77%). Three-month mortality rates were significantly higher among patients who had experienced an ICH event (39.4%; 95% CI: 35.4-43.8%), as opposed to patients without ICH (5.9%; 95% CI: 4.2-8.3%). This difference prevailed during follow-up, while mortality increased at roughly equal rates in both patient groups. Patients with ICH were on average hospitalised for 40.4 days/PY (95% CI: 35.7 days - 45.2 days) in the first year after the event; comparable patients without ICH were hospitalised for 10.8 days/PY (95% CI: 8.3 days - 13.2 days). Annual total costs per patient were €37,328 (95% CI: €32,243-€42,412) for patients with ICH, and €10,564 (95% CI: €9,298-€11,831) for patients without ICH. Hospitalisation costs were the main driver with 86.1% versus 50.8%, respectively.
Incidence rates of ICH during oral FXai therapy were within the range of other published real-world data. Duration of hospitalisations, associated costs, and mortality were high and significantly higher for patients with ICH than for comparable patients without ICH. The high burden on the healthcare system highlights the need for preventive measures and more efficient treatment pathways for patients with ICH under oral FXai therapy.
颅内出血（ICH）是口服Xa因子抑制剂（FXai）抗凝治疗最严重的并发症之一。为满足优化治疗途径这一迫切的医疗需求，我们评估了口服FXai治疗期间ICH的发生率，以及其给德国医疗保健系统带来的相关负担。
我们的研究基于一个包含德国400多万法定医疗保险参保人的理赔数据库。该研究纳入了2016年至2021年期间首次开始口服FXai治疗且在三年治疗期内发生ICH的患者。为了对住院、费用和死亡率进行均衡比较，对发生ICH和未发生ICH的患者进行了倾向评分匹配。
在研究期间，78,086名患者开始了口服FXai治疗，其中530名在治疗期间发生了ICH。在随访期间，口服FXai治疗开始后的前90天内ICH发生率最高，每100患者年（PY）有0.64例事件（95%置信区间：0.52 - 0.77%）。发生ICH事件的患者三个月死亡率显著更高（39.4%；95%置信区间：35.4 - 43.8%），而未发生ICH的患者死亡率为5.9%（95%置信区间：4.2 - 8.3%）。这种差异在随访期间持续存在，而两组患者的死亡率以大致相同的速度上升。ICH患者在事件发生后的第一年平均住院时间为40.4天/PY（95%置信区间：35.7天 - 45.2天）；未发生ICH的可比患者住院时间为10.8天/PY（95%置信区间：8.3天 - 13.2天）。ICH患者的人均年度总成本为37,328欧元（95%置信区间：32,243欧元 - 42,412欧元），未发生ICH的患者为10,564欧元（95%置信区间：9,298欧元 - 11,831欧元）。住院费用是主要驱动因素，分别占86.1%和50.8%。
口服FXai治疗期间ICH的发生率在其他已发表的真实世界数据范围内。住院时间、相关费用和死亡率都很高，ICH患者比未发生ICH的可比患者显著更高。医疗保健系统的高负担凸显了对接受口服FXai治疗的ICH患者采取预防措施和更有效治疗途径的必要性。
