AIM: New ischemic lesions in the brain can be detected in approximately 50% of patients undergoing carotid artery stenting (CAS). We wished to discover the laboratory-based predictors of new infarctions in the brain after CAS. METHODS: All consecutive patients with internal carotid artery stenosis of ≥70% with indication for CAS were enrolled in a prospective study for 16 months. All patients used dual antiplatelet therapy for ≥7 days before CAS. Neurologic examination and magnetic resonance imaging (MRI) of the brain were undertaken before and at 24 h after CAS. Samples of venous blood were collected at <24 h before CAS for the evaluation of hematology, reticulocytes, coagulation markers (PT, APTT, Fbg, Clauss), vWF antigen, PAI-1 activity, PAI-1 polymorphism 4G/5G, and the multiplate (aspirin and clopidogrel) resistance test. Blood samples for the assessment of anti-Xa activity were collected during CAS. Differences in the values of laboratory markers between patients with and without new ischemic lesions of the brain on control MRI were evaluated. RESULTS: The cohort comprised 81 patients (53 males; mean age, 67.3±7.2 years). New ischemic infarctions in the brain on control MRI were found in 46 (56.8%) patients. Three of seven patients with resistance to aspirin or clopidogrel had a new ischemic infarction in the brain. No significant differences for particular markers were found between patients with and without an ischemic lesion in the brain. CONCLUSION: A high risk of a new ischemic infarction in the brain was detected in patients undergoing CAS, but a laboratory-based predictor of such an infarction could not be identified.
- MeSH
- biologické markery analýza MeSH
- CT angiografie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mozkový infarkt diagnóza etiologie metabolismus MeSH
- prospektivní studie MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stenóza arteria carotis komplikace chirurgie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND PURPOSE: Granulocyte colony-stimulating factor (G-CSF; AX200; Filgrastim) is a stroke drug candidate with excellent preclinical evidence for efficacy. A previous phase IIa dose-escalation study suggested potential efficacy in humans. The present large phase IIb trial was powered to detect clinical efficacy in acute ischemic stroke patients. METHODS: G-CSF (135 µg/kg body weight intravenous over 72 hours) was tested against placebo in 328 patients in a multinational, multicenter, randomized, and placebo-controlled trial (NCT00927836; www.clinicaltrial.gov). Main inclusion criteria were ≤9-hour time window after stroke onset, infarct localization in the middle cerebral artery territory, baseline National Institutes of Health Stroke Scale score range of 6 to 22, and baseline diffusion-weighted imaging lesion size ≥15 mL. Primary and secondary end points were the modified Rankin scale score and the National Institutes of Health Stroke Scale score at day 90, respectively. Data were analyzed using a prespecified model that adjusted for age, National Institutes of Health Stroke Scale score at baseline, and initial infarct volume (diffusion-weighted imaging). RESULTS: G-CSF treatment failed to meet the primary and secondary end points of the trial. For additional end points such as mortality, Barthel index, or infarct size at day 30, G-CSF did not show efficacy either. There was, however, a trend for reduced infarct growth in the G-CSF group. G-CSF showed the expected peripheral pharmacokinetic and pharmacodynamic profiles, with a strong increase in leukocytes and monocytes. In parallel, the cytokine profile showed a significant decrease of interleukin-1. CONCLUSIONS: G-CSF, a novel and promising drug candidate with a comprehensive preclinical and clinical package, did not provide any significant benefit with respect to either clinical outcome or imaging biomarkers. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00927836.
- MeSH
- časové faktory MeSH
- cévní mozková příhoda * farmakoterapie metabolismus radiografie MeSH
- difuzní magnetická rezonance metody MeSH
- dospělí MeSH
- faktor stimulující kolonie granulocytů * aplikace a dávkování škodlivé účinky farmakokinetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mozkový infarkt * farmakoterapie metabolismus radiografie MeSH
- rekombinantní proteiny aplikace a dávkování škodlivé účinky farmakokinetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- MeSH
- degenerace nervu metabolismus patologie MeSH
- finanční podpora výzkumu jako téma MeSH
- ischemie mozku metabolismus patofyziologie patologie MeSH
- mozkový infarkt metabolismus patofyziologie patologie MeSH
- přivykání k ischémii MeSH
- pyramidové buňky metabolismus patologie MeSH
- železo metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
