International Stroke Conference 2006

The International Stroke Conference is an annual meeting held by the American Stroke Association, a division of the American Heart association, to create a platform to discuss all aspects of stroke care, with the primary aim of reducing disability and death from stroke. Topics encompass all aspects of stroke care: prevention, acute treatment, public health issues, in-hospital treatment, diagnostic imaging and rehabilitation. Leading scientists and clinicians from all round the world participate in the conference, held this year at Kissimmee, Florida, USA, 16–18th February.

Acute stroke therapy

Preliminary results of the Interventional Management of Stroke (IMS) II trial were presented by the IMS II group investigators. The trial investigated the feasibility and safety of a combined intravenous (IV) and intra-arterial (IA) approach to recanalization in patients with ischemic stroke. Patients were administered IV recombinant tissue plasminogen activator (rt-PA) within 3 h of stroke onset. Patients with eligible clot in extra- or intra-cranial cerebral vessels were subsequently administered IA rt-PA and low-energy ultrasound energy at the clot site, using the EKOS ultrasound catheter, for a maximum of 2 h of infusion or until thrombolysis was achieved. Comparisons were made with similar subsets of placebo and rt-PA treated subjects from the National Institute of Neurological Diseases and Stroke (NINDS) rt-PA Stroke Trial and subjects from IMS I. Results demonstrated that the combined IV and IA approach to recanalization was feasible and safe, and a trial comparing IV rt-PA with IV plus IA thrombolysis is being planned.

Results of the Diffusion-weighted imaging Evaluation For Understanding Stroke Evolution (DEFUSE) study were presented by Greg Albers from Stanford University (CA, USA). The study tested the hypothesis that specific magnetic resonance imaging patterns can identify patients who are most likely to benefit from early reperfusion. Early reperfusion was associated with a favorable clinical response in diffusion–perfusion mismatch patients. Patients without mismatch did not appear to benefit. Patients were treated with IV rt-PA in the 3–6 h window. The DEFUSE results support the concept that MRI patterns can differentiate patients who will benefit from early reperfusion from those who will not benefit or may be harmed.

A whole session was dedicated to the results of the stroke-acute-ischaemic-NXY-treatment (SAINT) I trial, which were recently published in the New England Journal of Medicine[1]. The randomized, double-blinded, placebo trial demonstrated that administration of NXY-059 within 6 h of the onset of acute ischemic stroke significantly improved the primary outcome (reduced disability at 90 days), but it did not significantly improve other outcome measures, including neurological functioning as measured by the National Institute of Health Stroke Scale score. No major complications were seen with NXY-059. Patients who received IV rt-PA plus NXY-059 had a significantly lower risk of symptomatic intracerebal hemorrhage than did patients who received rt-PA with placebo. A confirmatory Phase III trial, SAINT II trail, is presently recruiting patients and if results of SAINT II mirror the SAINT I trial, there is potential for a neuroprotective agent in the treatment of acute ischemic stroke.

Stroke prevention

Yukito Shinohara presented the results of the Sarpogrerale-Aspirin Comparative Clinical study for Efficacy and Safety in Secondary prevention of cerebral infarction (S-ACCESS) trial, a randomized, double-blind trial. Although sarpogrelate did not meet the predefined criterion of noninferiority to aspirin for efficacy against recurrence of cerebral infarction, it was better tolerated than aspirin, with significantly fewer bleeding events.

Two presentations regarding 1-year follow-up results of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) were presented. The trial is successfully enrolling patients. On behalf of the CREST investigators, Helmi Lutsep presented the results of restenois from the lead-in phase of CREST. Restenosis of 50% or more, as measured by ultrasound, developed in 22% of patients. This result is comparable to the 20% restenosis rate seen at 1 year in the Carotid Artery Stenting (CAS) arm of the Stenting and Angioplasty with Protection in Patients at HIgh Risk for Endarterectomy (SAPPHIRE) trial. Data were also presented measuring the 30-day stroke and mortality outcomes of the credentialing phase of CAS cases from the lead-in phase of the CREST trial. The 30-day stroke and death rate for symptomatic patients was similar to rates reported for carotid endarterectomy (CEA) in symptomatic randomized controlled trials. For asymptomatic patients, despite inclusion of higher-risk subsets (>80 years old) and more rigorous stroke detection methodology, the 30-day stroke and death rate for CAS was only slightly higher than that reported for CEA in asymptomatic randomized controlled trials.

Hemorrhage

Data were presented from three randomized, placebo-controlled studies of rFVIIa in intracerebral hemorrhage (ICH) patients (mean age 65) diagnosed within 3 h of onset. Subjects received a single dose of rFVIIa (5–160 µg/kg; n = 371) or placebo (n = 115). Pooled data demonstrated no significant differences in adverse effects between rFVIIa-dosed patients and those treated with placebo. Thromboembolic serious adverse events did not differ between treatment and placebo groups, with no increases in the risk for deep vein thrombosis (DVT) and/or pulmonary embolism, despite concerns. However, in the 160 µg/kg group, the frequency of arterial events was significantly greater than in the placebo group.

In-hospital guidelines

Lee H Schwamm presented data regarding the degree of improvement in acute stroke care and secondary prevention due to the national rollout of Get With The Guidelines (GWTG)-stroke, a hospital-based stroke quality improvement program. Clinically and statistically significant improvement occurred in all measures, except for rate of ICH after IV rt-PA, which did not increase, and DVT prophylaxis, which declined modestly. Measures included: use of IV rt-PA; symptomatic ICH; early antithrombotics or DVT prophylaxis and discharge antithrombotics; anticoagulation for atrial fibrillation; treatment for low density lipoprotein of more than 100; diabetes mellitus and counseling for smoking cessation; and obesity.

The University of California Irvine Medical Center (UCIMC) was in the initial group of hospitals certified by the Joint Commission on Accreditation of Health Care Organizations (JCAHO) as a primary Stroke Center. They presented their trends in stroke care delivery for the 1.5 years following, contrasted with the 3 years preceding, JCAHO certification. Since JCAHO Stroke Center certification, admission rates have increased for all stroke subtypes, particularly for patients with intracerebral hemorrhage, among whom length of stay has increased as well. Stroke Center certification was associated with improved rates of DVT prophylaxis, lipid panel testing and thrombolytic administration.

Other studies presented that generated interest included a study by the Northern Manhattan Study group looking at lipoprotein-associated phospholipase A₂ (LP-PLA₂) and highly sensitive C-reactive protein (HsCRP) as predictors of stroke recurrence and death. This study demonstrated that LP-PLA₂ may be a stronger predictor of recurrent stroke risk and that HsCRP, an acute phase reactant, increases with stroke severity and may predict mortality better than recurrence.

In the late-breaking session, results of the Clot Lysis: Evaluating Accelerated Resolution of IntraVentricular Hemorrhage (CLEAR IVH) study and the EXErcise Constraint Induced Therapy Evaluation (EXCITE) study were presented.

Dr Hanley presented results of the CLEAR study, a Phase II study investigating intraventricular rt-PA in patients with intraventricular hemorrhages. A total of 16 patients treated with either 0.3 mg or 1 mg of rt-PA delivered by intraventricular catheter had faster clot evacuation without an increased risk of bleeding or death. The symptomatic bleeding for both doses was zero and the mortality rate was 13%, compared with an historical mortality rate of 50%. Intraventricular rt-PA was safe and effective and a further Phase III study is being planned. The EXCITE investigators found that patients who underwent exercise constraint-induced therapy did better than those who did not receive constraint therapy.

The International Stroke Conference, 2006 was very well rounded. Cerebrovascular neurology has an exciting time ahead as thrombolysis options beyond intravenous tissue plasminogen are being studied and one also looks forward to the SAINT II trial investigating a neuroprotective agent (NXY 059) for acute ischemic stroke. The CREST trial is successfully enrolling patients. There is potential with rFVIIa for treating intracerebral hemorrhage and new potential treatment options of stroke rehabilitation.