Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Stroke. 2012 Jun;43(6):1561-6. doi: 10.1161/STROKEAHA.111.642322. Epub 2012 Apr 3.
Desmoteplase is a novel and highly fibrin-specific thrombolytic agent. Evidence of safety and efficacy was obtained in 2 phase II trials (Desmoteplase In Acute Ischemic Stroke [DIAS] and Desmoteplase for Acute Ischemic Stroke [DEDAS]). The DIAS-2 phase III trial did not replicate the positive phase II efficacy findings. Post hoc analyses were performed with the aim of predicting treatment responders based on CTA and MRA.
Patients were grouped according to vessel status (Thrombolysis In Myocardial Infarction [TIMI] grade) for logistic regression of clinical response, applying the data from DIAS-2 as well as the pooled data from DIAS, DEDAS, and DIAS-2.
In DIAS-2, a substantial number of mismatch-selected patients (126/179; 70%) presented with a normal flow/low-grade stenosis (TIMI 2-3) at screening, with the majority having a favorable outcome at day 90. In contrast, favorable outcome rates in patients with vessel occlusion/high-grade stenosis (TIMI 0-1) were 18% with placebo versus 36% and 27% with desmoteplase 90 and 125 μg/kg, respectively. The clinical effect based on the pooled data from DIAS, DEDAS, and DIAS-2 was favorable for desmoteplase-treated patients presenting with TIMI 0 to 1 at baseline (OR, 4.144; 95% CI, 1.40-12.23; P=0.010). There was no desmoteplase treatment benefit in patients presenting with TIMI 2 to 3 (OR, 1.109).
In this sample of patients with a mismatch diagnosed, proximal vessel occlusion or severe stenosis was associated with clinically beneficial treatment effects of desmoteplase. Selecting patients using CTA or MRA in clinical trials of thrombolytic therapy is justifiable.
Desmoteplase 是一种新型的、高度纤维蛋白特异性溶栓药物。两项 II 期临床试验（Desmoteplase In Acute Ischemic Stroke [DIAS] 和 Desmoteplase for Acute Ischemic Stroke [DEDAS]）证实了其安全性和有效性。然而，DIAS-2 期 III 期试验并未复制阳性的 II 期疗效发现。本研究进行了事后分析，旨在根据 CTA 和 MRA 预测治疗反应者。
根据血管状态（Thrombolysis In Myocardial Infarction [TIMI] 分级）将患者分组，对 DIAS-2 的临床反应进行逻辑回归分析，并应用 DIAS-2、DIAS、DEDAS 和 DIAS-2 的汇总数据。
在 DIAS-2 中，大量错配选择的患者（179 例中的 126 例；70%）在筛选时表现为正常血流/低级别狭窄（TIMI 2-3），其中大多数在第 90 天有良好的结局。相比之下，血管闭塞/高级别狭窄（TIMI 0-1）患者的安慰剂组、90μg/kg 和 125μg/kg desmoteplase 组的良好结局率分别为 18%、36%和 27%。基于 DIAS、DEDAS 和 DIAS-2 的汇总数据，基线时 TIMI 0 至 1 的 desmoteplase 治疗患者的临床效果较好（OR，4.144；95%CI，1.40-12.23；P=0.010）。TIMI 2 至 3 的患者没有 desmoteplase 治疗获益（OR，1.109）。
在诊断为错配的患者样本中，近端血管闭塞或严重狭窄与 desmoteplase 的临床获益治疗效果相关。在溶栓治疗临床试验中使用 CTA 或 MRA 选择患者是合理的。
