Kalinin M N, Khasanova D R
Kazan State Medical University, Kazan, Russia.
Interregional Clinical Diagnostic Center, Kazan, Russia.
Zh Nevrol Psikhiatr Im S S Korsakova. 2024;124(3. Vyp. 2):55-66. doi: 10.17116/jnevro202412403255.
The study goal was the assessment of heterogeneous treatment effects of Cerebrolysin as an early add-on to reperfusion therapy in stroke patients with varying risk of hemorrhagic transformation (HT).
It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744). Patients with middle cerebral artery infarction (=238) were stratified by HT risk with the HTI score. The study outcomes were symptomatic and any HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90. Favorable outcome was defined as an mRS score of ≤2. Heterogeneous treatment effect analysis was performed using techniques of meta-analysis and the matching-smoothing method.
Heterogeneity of Cerebrolysin treatment effects was moderate (I=36.98-69.3%, H=1.59-3.26) and mild (I=18.33-32.39%, H=1.22-1.48) for symptomatic and any HT, respectively. A positive impact of the Cerebrolysin treatment on HT and functional outcome was observed in patients with moderate (HTI=1) and high (HTI≥2) HT risk. However, the effect was neutral in those with low risk (HTI=0). In high HT risk patients, there was a steady decline in the rate of symptomatic (HTI=0 vs. HTI≥2: by 3.8%, =0.120 vs. 14.3%, <0.001) and any HT (HTI=0 vs. HTI≥2: by 0.6%, =0.864 vs. 19.5%, <0.001). Likewise, Cerebrolysin treatment resulted in an overall decrease in the mRS scores (HTI=0 vs. HTI≥2: by 2.1%, =0.893 vs. 63%, <0.001) with a reciprocal increase of the fraction with favorable outcome (HTI=0 vs. HTI≥2: by 2% =0.634 vs. 19.2%, <0.001).
Clinically meaningful heterogeneity of Cerebrolysin treatment effects on HT and functional outcome was established in stroke patients. The Cerebrolysin positive impact was significant in those whose estimated on-admission HT risk was either moderate or high.
本研究旨在评估脑蛋白水解物作为再灌注治疗的早期附加治疗对具有不同出血转化（HT）风险的中风患者的异质性治疗效果。
这是对CEREHETIS试验（ISRCTN87656744）的事后分析。将大脑中动脉梗死患者（=238例）根据HT风险用HTI评分进行分层。研究结局为有症状的HT和任何HT，以及在第90天用改良Rankin量表（mRS）测量的功能结局。良好结局定义为mRS评分≤2。使用荟萃分析技术和匹配平滑法进行异质性治疗效果分析。
脑蛋白水解物治疗效果的异质性对于有症状的HT为中度（I=36.98 - 69.3%，H=1.59 - 3.26），对于任何HT为轻度（I=18.33 - 32.39%，H=1.22 - 1.48）。在中度（HTI=1）和高度（HTI≥2）HT风险的患者中观察到脑蛋白水解物治疗对HT和功能结局有积极影响。然而，在低风险（HTI=0）患者中效果为中性。在高HT风险患者中，有症状的HT发生率（HTI=0 vs. HTI≥2：从3.8%降至14.3%，P=0.120 vs. <0.001）和任何HT发生率（HTI=0 vs. HTI≥2：从0.6%降至19.5%，P=0.864 vs. <0.001）稳步下降。同样，脑蛋白水解物治疗导致mRS评分总体下降（HTI=0 vs. HTI≥2：从2.1%降至63%，P=0.893 vs. <0.001），同时良好结局比例相应增加（HTI=0 vs. HTI≥2：从2%升至19.2%，P=0.634 vs. <0.001）。
在中风患者中确定了脑蛋白水解物治疗效果对HT和功能结局具有临床意义的异质性。脑蛋白水解物的积极影响在入院时估计HT风险为中度或高度的患者中显著。
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