Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Service de Biostatistique, Hospices Civils de Lyon, Lyon, France.
Eur J Neurol. 2021 Feb;28(2):532-539. doi: 10.1111/ene.14566. Epub 2020 Oct 28.
Polypharmacy is an important challenge in clinical practice. Our aim was to determine the effect of polypharmacy on functional outcome and treatment effect of alteplase in acute ischaemic stroke.
This was a post hoc analysis of the randomized, placebo-controlled WAKE-UP trial of magnetic resonance imaging guided intravenous alteplase in unknown onset stroke. Polypharmacy was defined as an intake of five or more medications at baseline. Comorbidities were assessed by the Charlson Comorbidity Index (CCI). The primary efficacy variable was favourable outcome defined by a score of 0-1 on the modified Rankin Scale at 90 days. Logistic regression analysis was used to test for an association of polypharmacy with functional outcome, and for interaction of polypharmacy and the effect of thrombolysis.
Polypharmacy was present in 133/503 (26%) patients. Patients with polypharmacy were older (mean age 70 vs. 64 years; p < 0.0001) and had a higher score on the National Institutes of Health Stroke Scale at baseline (median 7 vs. 5; p = 0.0007). A comorbidity load defined by a CCI score ≥ 2 was more frequent in patients with polypharmacy (48% vs. 8%; p < 0.001). Polypharmacy was associated with lower odds of favourable outcome (adjusted odds ratio 0.50, 95% confidence interval 0.30-0.85; p = 0.0099), whilst the CCI score was not. Treatment with alteplase was associated with higher odds of favourable outcome in both groups, with no heterogeneity of treatment effect (test for interaction of treatment and polypharmacy, p = 0.29).
In stroke patients, polypharmacy is associated with worse functional outcome after intravenous thrombolysis independent of comorbidities. However, polypharmacy does not interact with the beneficial effect of alteplase.
药物滥用是临床实践中的一个重要挑战。我们的目的是确定药物滥用对急性缺血性脑卒中患者接受阿替普酶静脉溶栓后的功能结局和治疗效果的影响。
这是一项针对磁共振成像指导下静脉使用阿替普酶治疗不明原因起病脑卒中的随机、安慰剂对照 WAKE-UP 试验的事后分析。药物滥用定义为基线时服用五种或更多种药物。共病情况采用 Charlson 共病指数（CCI）评估。主要疗效变量为 90 天时改良 Rankin 量表评分为 0-1 的良好结局。采用 logistic 回归分析检验药物滥用与功能结局之间的关联，并检验药物滥用与溶栓效果之间的交互作用。
503 例患者中 133 例（26%）存在药物滥用。药物滥用组患者年龄更大（平均年龄 70 岁 vs. 64 岁；p<0.0001），基线时 NIHSS 评分更高（中位数 7 分 vs. 5 分；p=0.0007）。药物滥用组的共病负担（CCI 评分≥2）更常见（48% vs. 8%；p<0.001）。药物滥用与良好结局的可能性较低相关（校正比值比 0.50，95%置信区间 0.30-0.85；p=0.0099），而 CCI 评分与良好结局无关。阿替普酶治疗与两组患者良好结局的可能性增加相关，且治疗效果无异质性（检验治疗与药物滥用之间的交互作用，p=0.29）。
在脑卒中患者中，药物滥用与静脉溶栓后功能结局较差独立相关，与共病无关。然而，药物滥用与阿替普酶的治疗效果没有交互作用。
