The Abciximab in Emergent Stroke Treatment Trial (AbESTT) examined the anticlotting drug abciximab in a randomized, double-blind, placebo-controlled study of 400 patients with ischemic stroke. Safety and efficacy were assessed at three months for abciximab in patients with planned treatment within six hours of stroke onset. The primary safety end point was a composite of fatal intracranial hemorrhage, nonfatal symptomatic parenchymal hemorrhage, or other symptomatic intracranial hemorrhage through discharge (or the fifth day, if earlier). “We looked at efficacy, at three months, because we wanted to have some hint as to whether or not we should go on to a large clinical trial,” said Harold P. Adams Jr, MD, of the University of Iowa Hospitals and Clinics in Iowa City.

A total of 195 patients received abciximab, and 199 received placebo. The researchers found that 9% of actively treated patients died during the three-month follow-up period versus 12.5% of patients on placebo. Seven patients (3.6%) on abciximab had symptomatic intracranial hemorrhage through discharge or day 5, versus two (1%) in the placebo group. Eight patients (4.1%) on abciximab had total symptomatic intracranial hemorrhage through three months, versus two (1%) on placebo. A total of 24 patients (12.3%) who received abciximab had asymptomatic intracranial hemorrhage through three months, versus 33 patients (16.6%) taking placebo.

“We believe that our trial has demonstrated that this agent can be given with a reasonable degree of safety to a broad spectrum of patients with acute ischemic stroke,” said Dr. Adams. “We treated patients largely in the time period of three to six hours. We also think that there’s a strong trend that this agent can improve outcomes after ischemic stroke. It appears that we have the best chance for success for patients treated within five hours and for those patients with mild to moderate neurologic impairments at baseline. Because we don’t have much else for patients in the zero- to six-hour window, and because this agent appears to be safe and possibly effective, we believe further study of the agent is clearly warranted.”

Furthermore, Dr. Adams commented, “t-PA [tissue plasminogen activator] is effective, but it is not very useful. We need other alternatives for treatment of patients with stroke. We need more therapies that are patient and doctor friendly. We need to be able to treat more patients.”

THE SSYLVIA TRIAL

According to Helmi L. Lutsep, MD, the rate of stroke for patients taking drugs to treat narrowing in a major brain artery is 10% to 24% per year. She and her colleagues launched the Stenting of Symptomatic Atherosclerotic Lesions in the Vertebral or Intracranial Arteries (SSYLVIA) trial. This multicenter, nonrandomized prospective study evaluated the treatment of vertebral or intracranial artery stenosis.

Patients were ages 19 to 80 and had symptoms attributed to the target lesion. Angiographic criteria required a single target lesion of 50% or greater stenosis. All participants received five neurologic examinations prior to and in the year after the procedure. The investigators examined the effectiveness of a stainless steel stenting device designed for the neurovasculature that provides blood vessel structural support. It was used in treating narrowed brain arteries, either the vertebral artery before it enters the skull or those in the brain of patients with symptoms due to these narrowings.

Sixty-one patients were enrolled, and 60 were treated. A total of 43 patients (70.5%) had a narrowed intracranial artery, and 18 (29.5%) had a narrowed extracranial vertebral artery. Stents were successfully placed in 95% of the patients. Within the first 30 days, four patients (6.6%) had a nonfatal stroke, and no deaths occurred. At six months, arteries in 34% of patients with brain artery narrowing had renarrowed by more than 50%. Half of patients with narrowed extracranial vertebral arteries had renarrowing of 50% or more in six months. Of those followed up at 12 months, four (9.5%) had a stroke later than one month after stent placement, one of whom was the only patient not stented.

“The [stent] procedure is safe and feasible,” said Dr. Lutsep, who is the Associate Director of the Oregon Stroke Center at Oregon Health and Science University, Portland. “There is a high rate of successful stent deployment and relatively low rates of stroke at 30 days, and the longer follow-up is encouraging. Although there is this 34% intracranial restonosis rate at six months, the great majority of these patients did not have strokes. Further trials are warranted.” The FDA has granted a Humanitarian Device Exemption for this stent system.

THE SAPPHIRE STUDY

The Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) study compared carotid stenting with distal protection against endarterectomy in high-risk surgical patients, said Pierre Fayad, MD. The study included 723 patients; follow-up occurred at 30 days, six months, one year, and annually afterward. The results presented were for the first 30 days of follow-up, while the one-year follow-up is pending. The key inclusion criteria mandated the presence of 1) carotid stenosis of more than 50% for symptomatic patients and more than 80% for asymptomatic patients; 2) it had to be a native, common, or internal carotid artery; 3) the patients needed to additionally have one or more risk factors that placed them at high surgical risk; and 4) a consensus was required among neurologists, interventionalists, and a surgeon to allocate those patients. The key exclusion criteria were acute ischemic stroke within 48 hours, total occlusion of the target artery, and a need for intervention—whether surgical or procedural—within the next 30 days.

For all 307 patients randomized, 5.8% of those randomized to stenting with emboli protection suffered death, stroke, or myocardial infarction, compared with 12.6% of those randomized to treatment with carotid endarterectomy within the first 30 days. A total of 409 patients, rejected for surgery and enrolled in the stent registry, had a 7.8% 30-day rate of major adverse clinical events (MACE) encompassing death, stroke, or myocardial infarction. In addition, seven patients were denied stenting and enrolled in the surgical registry, one of whom had a 30-day MACE.

“This is the first randomized study that compared carotid stenting with emboli protection to carotid endarterectomy and that exclusively looked at high-risk patients and included myocardial infarction as part of the primary outcomes,” said Dr. Fayad, who is the Reynolds Centennial Professor and Chairman of the Department of Neurological Sciences at the University of Nebraska Medical Center in Omaha. “It is the first randomized study that shows a significantly lower 30-day MACE for stenting with an endovascular protective device than for carotid endarterectomy. The results also show a consistently favorable trend for stenting in asymptomatic or symptomatic patients for each individual primary end point and for inpatient and out-of-hospital events.”

Dr. Fayad also noted that the investigators achieved a greater than 98% success rate in deploying, and retrieving the distal protection device. “The results demonstrated also the excellent technical success for deploying the stent in more than 90% of patients, whether in the randomized or the registry arm.”

NR

—Colby Stong

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