TY - JOUR
T1 - Vascular occlusion enables selecting acute ischemic stroke patients for treatment with desmoteplase
AU - Fiebach, Jochen B.
AU - Al-Rawi, Yasir
AU - Wintermark, Max
AU - Furlan, Anthony J.
AU - Rowley, Howard A.
AU - Lindstén, Annika
AU - Smyej, Jamal
AU - Eng, Paul
AU - Warach, Steven
AU - Pedraza, Salvador
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/6
Y1 - 2012/6
N2 - Background and Purpose-: 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. Methods-: 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. Results-: 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). Conclusions-: 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. Clinical Trial Registration INFORMATION-: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00638781, NCT00638248, NCT00111852.
AB - Background and Purpose-: 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. Methods-: 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. Results-: 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). Conclusions-: 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. Clinical Trial Registration INFORMATION-: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00638781, NCT00638248, NCT00111852.
KW - computed tomography angiography
KW - desmoteplase
KW - magnetic resonance angiography
KW - occlusion
KW - stroke
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U2 - 10.1161/STROKEAHA.111.642322
DO - 10.1161/STROKEAHA.111.642322
M3 - Article
C2 - 22474060
AN - SCOPUS:84861580849
SN - 0039-2499
VL - 43
SP - 1561
EP - 1566
JO - Stroke
JF - Stroke
IS - 6
ER -