title: Vascular occlusion enables selecting acute ischemic stroke patients for treatment with desmoteplase.
abstract: OBJECTIVE
  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.
authors.affiliation: Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany. jochen.fiebach@charite.de
authors.forename: Jochen B
authors.initials: JB
authors.lastname: Fiebach
authors.forename: Yasir
authors.initials: Y
authors.lastname: Al-Rawi
authors.forename: Max
authors.initials: M
authors.lastname: Wintermark
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Furlan
authors.forename: Howard A
authors.initials: HA
authors.lastname: Rowley
authors.forename: Annika
authors.initials: A
authors.lastname: Lindstén
authors.forename: Jamal
authors.initials: J
authors.lastname: Smyej
authors.forename: Paul
authors.initials: P
authors.lastname: Eng
authors.forename: Steven
authors.initials: S
authors.lastname: Warach
authors.forename: Salvador
authors.initials: S
authors.lastname: Pedraza
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology*; D003251:Constriction, Pathologic / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010960:Plasminogen Activators / Q000008:administration & dosage* / Q000009:adverse effects; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D005343:Fibrinolytic Agents; C069588:salivary plasminogen activator alpha 1, Desmodus rotundus; D010960:Plasminogen Activators