XVII. European Stroke Conference
Nice, France

Oral Session:

Large clinical trials  (RCTs)  II
Date: Friday 16 May 2008  
Time: 11:00 - 11:10 -  Room: Apollon
Chair: S. Davis, Australia and G.-L. Lenzi, Italy

01
Carotid restenosis after endovascular therapy or endarterectomy in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS) – 8 years follow-up
L.H.Bonati    J. Ederle    J. Dobson    R.L.Featherstone    M.M.Brown                                   
CAVATAS Investigators

Stroke Research Group, Department of Brain Repair and Rehabilitation, UCL Intstitute of Neurology

UNITED KINGDOM

Background: In the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS) restenosis of the carotid artery was more common one year after endovascular treatment than after endarterectomy. We investigated whether this difference persisted during follow-up, how restenosis contributed to recurrent ischaemic events, and which factors predicted restenosis. Methods: High grade (>/=70%) carotid restenosis or carotid occlusion diagnosed by ultrasound after successful endovascular treatment (n=196) or endarterectomy (n=217) of carotid stenosis was compared during a follow-up of up to 8 years (mean 4.1+/-2.5 years). We examined the effect of gender, age, diabetes, blood pressure, hypercholesterolemia, smoking, ischaemic heart disease, peripheral vascular disease, and baseline degree of carotid stenosis on restenosis. Ipsilateral stroke, TIA and amaurosis fugax (AFX) during follow-up were compared between patients with and patients without >/=70% carotid stenosis or occlusion one year after treatment. Results: 53/196 patients (27%) in the endovascular group, and 18/217 patients (8%) in the endarterectomy group developed>/=70% carotid restenosis or occlusion (OR 3.6 [95% CI 2.1-6.2], p<0.0001). The proportion of patients with restenosis after endovascular treatment with the use of stents (7/50, 14%) did not differ significantly from endarterectomy. Smoking was an independent predictor of restenosis (OR 3.4 [1.2-9.0], p=0.002). Stroke, TIA or AFX occurred in 9/41 patients (22%) with >/=70% stenosis or occlusion and in 24/293 patients (8%) with <70% stenosis one year after treatment (OR 3.0 [1.4-6.4], p=0.005). However, the occurrence of stroke itself did not differ between patients with >/=70% and <70% stenosis (1/41, 2% and 12/293, 4%, respectively). Conclusions: High grade carotid restenosis or occlusion remained more frequent after endovascular therapy than after endarterectomy throughout the entire follow-up. High-grade restenosis or occlusion appears to cause TIA and AFX, but not stroke. The risk of restenosis is increased more than three times in smokers.

Large clinical trials  (RCTs)  II
Date: Friday 16 May 2008  
Time: 11:10 - 11:20 -  Room: Apollon
Chair: S. Davis, Australia and G.-L. Lenzi, Italy

02
Asymptomatic Carotid Emboli Study (ACES): Baseline data
R. Topakian    J. Siegel    K. Jones    H.S.Markus                                          
for the ACES investigators

Clinical Neuroscience, St George’s University of London, London

UNITED KINGDOM

Background: Better methods of identifying which patients with asymptomatic carotid stenosis (ACS) develop stroke are required to improve risk-benefit ratios for endarterectomy. A promising method is detection of asymptomatic embolic signals (ES) using transcranial Doppler(TCD). ES predict stroke risk in symptomatic carotid stenosis but data in ACS is limited. Method: ACES is a prospective study in ACS >=70%. Two 1 hour ipsilateral MCA TCD recordings are performed at baseline, and a single hour recording at 6, 12, and 18 months. Follow up is 2 years and will complete in October 2009. All recordings are centrally analysed. The primary endpoint is: Do ES on either of 2 baseline recordings predict ipsilateral TIA and stroke over 2 years? Secondary endpoint: Do ES on a single hour long recording predict risk over any subsequent 6 month period? Power calculations were based on interim blinded data on the first 132 subjects: 21.2% had ES during either of 2 baseline TCDs; 12.1% had ES on the 1st of the 2 entry recordings. To detect a relative risk of 3 (power 0.9, p< 0.05) a sample size of 480 is required for the primary endpoint and 367 for secondary endpoint. Results: Recruitment completed October 2007 with 482 patients from 26 centres in 17 countries in Europe, Asia and USA. Baseline demographics were: mean age 71.5 years; hypertension 79%; smoking: current 14.5%, ex 46.5%; diabetes: 20.5%. Contralateral stenosis (>70%) 19.9%. Ultrasound plaque morphology on blinded central review: echolucent 10.9%, predominantly echolucent 26.8%, predominantly echogenic 35.7%, echogenic 11.1%, unclassifiable 15.5%. To date there have been 39 events in the study artery (12 stroke, 27 TIA /A fugax). Rates on prevalence of ES at baseline and their relationship to clinical parameters will be presented. Conclusions: ACES is the first multicentre international trial to determine whether ES is a useful predictor in ACS, and allow its predictive value to be compared with clinical and imaging parameters and ultrasound plaque morphology.

Large clinical trials  (RCTs)  II
Date: Friday 16 May 2008  
Time: 11:20 - 11:30 -  Room: Apollon
Chair: S. Davis, Australia and G.-L. Lenzi, Italy

03
AX 200 (G-CSF) for the treatment of acute ischemic stroke (AXIS)
W.R.Schäbitz    R. Laage    S.  Schwab    D. Schneider    G. Hamann    R. Kollmar    M. Rosenkranz    R. Veltkamp    M. Fisher    J. Grotta
W. Hacke A. Schneider for the AXIS study group

University of Münster

GERMANY

Background: The hematopoietic factor G-CSF (AX200) inhibits apoptotic cell death and stimulates neural progenitor differentiation in the ischemic brain. In a number of different animal stroke models G-CSF (AX200) robustly decreased infarct volume and enhanced functional recovery. To translate these experimental results into the clinic, a national, multicenter, randomized, placebo-controlled phase IIa trial (AXIS) was initiated in December 2004. Methods: G-CSF (AX200) was administered in 4 increasing doses (30, 90, 135, 180 µg/kg bodyweight over 72 h) as i.v. infusion (30 patients) and compared to placebo (14 patients) within a time window of 12 hours. Primary endpoints assessed potential thromboembolic complications and distribution of serious adverse events. Secondary endpoints included occurrence of severe infections, intracranial hemorrhage, or changes in hematocrit and thrombocyte count. Exploratory efficacy analyses aimed at clinical outcome (NIHSS, mRS, BI), and ischemic lesion volume based on MRI. Results: Baseline characteristics were similar between verum and placebo groups. The primary and secondary endpoints were reached. G-CSF (AX200) was generally well tolerated with no increase in serious adverse events. Importantly, stenoses of extra- and intracranial arteries were not negatively affected by G-CSF (AX200) treatment. Simple comparison of clinical or imaging outcome variables did not yield differences between placebo and verum groups. However, using age, NIHSS and diffusion volume at baseline as factors in an exploratory multiple regression model, we detected a positive influence of AX200 on all clinical outcome parameters in patients with larger strokes. Conclusion: Intravenous G-CSF (AX200) even at high doses is well tolerated in stroke patients. Exploratory efficacy analyses suggest a beneficial effect on neurological outcome in patients with larger strokes. The results of the AXIS study will serve as a valuable basis for the further clinical development of G-CSF (AX200) in ischemic stroke.