Low dosis of alteplase, for ischemic stroke after Enchanted and its determinants, a single center experience

Abstract Background: Low-dose alteplase (LrtPA) has been shown not to be inferior to the standard-dose (SrtPA) with respect to death/disability. Objective: We aim to evaluate the percentage of patients treated with LrtPA at our center after the ENCHANTED trial and the factors associated with the use of this dosage. Methods: Prospective study in consecutive patients with an acute stroke admitted between June 2016 and November 2018. Results: 160 patients were treated with intravenous thrombolysis, 50% female; mean age 65.4±18.5 years. Of these, 48 patients (30%) received LrtPA. In univariate analysis, LrtPA was associated with patient's age (p=0.000), previous modified Rankin scale scores (mRS) (p<0.000), hypertension (p=0.076), diabetes mellitus (p=0.021), hypercholesterolemia (p=0.19), smoking (p=0.06), atrial fibrillation (p=0.10), history of coronary artery disease (p=0.06), previous treatment with antiplatelet agents (p<0.000), admission International Normalized Ratio-INR (p=0.18), platelet count (p=0.045), leukoaraiosis on neuroimaging (p<0.003), contraindications for thrombolytic treatment (p=0.000) and endovascular treatment (p=0.027). Previous relevant bleedings were determinants for treatment with LrtPA. Final diagnosis on discharge of stroke mimic was significant (p=0.02) for treatment with SrtPA. In multivariate analysis, mRS (OR: 2.21; 95%CI 1.37‒14.19), previous antiplatelet therapy (OR: 11.41; 95%CI 3.98‒32.70), contraindications for thrombolysis (OR: 56.10; 95%CI 8.81‒357.80), leukoaraiosis (OR: 4.41; 95%CI 1.37‒14.10) and diagnosis of SM (OR: 0.22; 95%CI 0.10‒0.40) remained independently associated. Conclusions: Following the ENCHANTED trial, LrtPA was restricted to 30% of our patients. The criteria that clinicians apply are based mostly on clinical variables that may increase the risk of brain or systemic hemorrhage or exclude the patient from treatment with lytic drugs.

Abstract 背景：已有研究证实，低剂量阿替普酶（low-dose alteplase，LrtPA）在死亡/残疾结局方面不劣于标准剂量阿替普酶（standard-dose alteplase，SrtPA）。
目的：本研究旨在评估ENCHANTED试验开展后，本中心采用LrtPA治疗的急性卒中患者占比，以及与该给药方案使用相关的影响因素。
方法：本研究为前瞻性研究，纳入2016年6月至2018年11月期间收治的连续性急性卒中患者。
结果：本研究共纳入160例接受静脉溶栓治疗的患者，其中女性占比50%，平均年龄为65.4±18.5岁。其中48例（30%）患者接受了LrtPA治疗。单因素分析结果显示，LrtPA的使用与患者年龄（p=0.000）、既往改良Rankin量表（modified Rankin scale，mRS）评分（p<0.000）、高血压（p=0.076）、糖尿病（p=0.021）、高胆固醇血症（p=0.19）、吸烟史（p=0.06）、心房颤动（p=0.10）、冠状动脉粥样硬化性心脏病病史（p=0.06）、既往抗血小板药物治疗史（p<0.000）、入院时国际标准化比值（international normalized ratio，INR）（p=0.18）、血小板计数（p=0.045）、神经影像学检出的脑白质疏松症（p<0.003）、溶栓治疗禁忌证（p=0.000）以及血管内治疗史（p=0.027）显著相关。既往出血史是患者接受LrtPA治疗的相关影响因素。出院时诊断为卒中模拟病（stroke mimic，SM）与SrtPA的使用显著相关（p=0.02）。多因素分析结果显示，既往mRS评分（比值比OR：2.21；95%置信区间CI：1.37‒14.19）、既往抗血小板治疗史（OR：11.41；95%CI：3.98‒32.70）、溶栓治疗禁忌证（OR：56.10；95%CI：8.81‒357.80）、脑白质疏松症（OR：4.41；95%CI：1.37‒14.10）以及卒中模拟病诊断（OR：0.22；95%CI：0.10‒0.40）仍与LrtPA的使用独立相关。
结论：ENCHANTED试验开展后，本中心仅30%的急性卒中患者接受了LrtPA治疗。临床医师所采用的给药选择标准主要基于可能增加颅内或全身出血风险、或会使患者无法接受溶栓药物治疗的临床变量。