Vascular occlusion enables selecting acute ischemic stroke patients for treatment with desmoteplase

Jochen B. Fiebach, Yasir Al-Rawi, Max Wintermark, Anthony J. Furlan, Howard A. Rowley, Annika Lindstén, Jamal Smyej, Paul Eng, Steven Warach, Salvador Pedraza

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1561-1566
Number of pages6
JournalStroke
Volume43
Issue number6
DOIs
StatePublished - Jun 2012

Fingerprint

Blood Vessels
Stroke
Myocardial Infarction
Therapeutics
Pathologic Constriction
salivary plasminogen activator alpha 1, Desmodus rotundus
Clinical Trials
Fibrinolytic Agents
Thrombolytic Therapy
Fibrin
Logistic Models
Placebos
Safety

Keywords

  • computed tomography angiography
  • desmoteplase
  • magnetic resonance angiography
  • occlusion
  • stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing

Cite this

Fiebach, J. B., Al-Rawi, Y., Wintermark, M., Furlan, A. J., Rowley, H. A., Lindstén, A., ... Pedraza, S. (2012). Vascular occlusion enables selecting acute ischemic stroke patients for treatment with desmoteplase. Stroke, 43(6), 1561-1566. https://doi.org/10.1161/STROKEAHA.111.642322

Vascular occlusion enables selecting acute ischemic stroke patients for treatment with desmoteplase. / Fiebach, Jochen B.; Al-Rawi, Yasir; Wintermark, Max; Furlan, Anthony J.; Rowley, Howard A.; Lindstén, Annika; Smyej, Jamal; Eng, Paul; Warach, Steven; Pedraza, Salvador.

In: Stroke, Vol. 43, No. 6, 06.2012, p. 1561-1566.

Research output: Contribution to journalArticle

Fiebach, JB, Al-Rawi, Y, Wintermark, M, Furlan, AJ, Rowley, HA, Lindstén, A, Smyej, J, Eng, P, Warach, S & Pedraza, S 2012, 'Vascular occlusion enables selecting acute ischemic stroke patients for treatment with desmoteplase', Stroke, vol. 43, no. 6, pp. 1561-1566. https://doi.org/10.1161/STROKEAHA.111.642322
Fiebach JB, Al-Rawi Y, Wintermark M, Furlan AJ, Rowley HA, Lindstén A et al. Vascular occlusion enables selecting acute ischemic stroke patients for treatment with desmoteplase. Stroke. 2012 Jun;43(6):1561-1566. https://doi.org/10.1161/STROKEAHA.111.642322
Fiebach, Jochen B. ; Al-Rawi, Yasir ; Wintermark, Max ; Furlan, Anthony J. ; Rowley, Howard A. ; Lindstén, Annika ; Smyej, Jamal ; Eng, Paul ; Warach, Steven ; Pedraza, Salvador. / Vascular occlusion enables selecting acute ischemic stroke patients for treatment with desmoteplase. In: Stroke. 2012 ; Vol. 43, No. 6. pp. 1561-1566.
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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

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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.

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KW - computed tomography angiography

KW - desmoteplase

KW - magnetic resonance angiography

KW - occlusion

KW - stroke

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