Prospective study of symptomatic atherothrombotic intracranial stenoses
The GESICA Study
Abstract
Background: Symptomatic intracranial atherothrombotic stenoses (ICAS) are associated with high rates of cerebrovascular ischemic events.
Objective: To conduct a prospective multicenter study to evaluate the natural history of ICAS and, in those patients refractory to medical treatment, the outcomes associated with intracranial angioplasty.
Methods: Patients aged 18 to 80 were enrolled with symptoms attributed to a single ICAS of ≥50%. Optimal medical therapy of vascular risk factors and preventive antithrombotic therapy were at the discretion of the local investigator. Patients were eligible for intracranial angioplasty after experiencing recurrent stroke despite medical therapy. Neurologic and ultrasonographic examinations were performed at study inclusion, 3 months after enrollment, and every 6 months of follow-up thereafter, for 36 months.
Results: One hundred two patients were included, with a mean age of 63.3 ± 10.4 years. Intracranial artery stenoses involved the vertebral artery in 22.5%, the basilar artery in 25.5%, the middle cerebral artery in 26.5%, and the internal carotid artery in 25.5%. In 27.4% of the patients, the stenoses had clinical hemodynamic characteristics. During a mean follow-up of 23.4 months, 38.2% of the patients had a cerebrovascular event: ischemic stroke in 13.7% and TIA in 24.5%. Among patients with a hemodynamically significant stenosis, 60.7% had a recurrent stroke or TIA in the territory of the stenotic artery; this association was significant in univariate analysis. Twenty-eight patients underwent an endovascular procedure with a neurologic periprocedural complication rate of 14.2%. The overall vascular death rate was 8.8%.
Conclusions: Despite medical treatment, the 2-year recurrence rate of ischemic events in the territory of the stenotic artery was 38.2%. Cardiovascular events occurred in 18.6% of patients. Clinically significant hemodynamic stenoses were associated with stroke recurrence and may help identify a high risk subset of patients.
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Published online: April 24, 2006
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I read with interest Mazighi et al's paper on the natural history of symptomatic intracranial stenosis. [1] Their population resembles that of the WASID trial regarding the risk factor profile. [2] However, the reported rates of cerebrovascular events are misleading considering the composite end point alone. The annual rate of cerebrovascular events was 19% (38% at two years) although the rate of TIA was twice as frequent as stroke (12% vs 7%). Additionally, two thirds of patients who underwent angioplasty did so following a TIA, and the peri-procedural rate of neurological complications was 14%.
The composite end point issue is important because one is the apparent magnitude of risk when the composite end point is considered alone and the other is the relative importance of the different component end points to patients, particularly in a situation when an invasive procedure becomes a treatment alternative and it is associated with a high periprocedural risk.
When presented with an annual risk of a cerebrovascular event of 19% and a treatment procedure with a complication rate of 14%, one may feel compelled to get the angioplasty. However, if the risk of stroke is considered alone (7%) we might decide for medical treatment. Even when TIA and stroke have the same biological mechanism and the very high early risk of stroke that TIA portends [3], it can be argued that for patients or physicians a TIA may have different importance as outcome.
This problem is illustrated with the VA Cooperative study on carotid endarterectomy. [4] In that trial, the benefit of the procedure was observed only when the composite end point included crescendo TIA and it was outweighed by the risks when TIA was not considered. Some authors recommended that to base a clinical decision on a composite event one has to determine: a) if the component end points are of similar importance to patients; b) if the end points occur with similar frequency; and c) if the expected risk reductions are similar with treatment.
When there are wide variations between the components then the composite end point should be abandoned. [5] Mazighi et al did not need the addition of TIA to represent the high risk these patients carry. Moreover, death was a better component of a composite end point. I commend the authors' restraint on recommending angioplasty or stent placement and acknowledging the need for further clinical trials.
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2.Chimowitz MI, Lynn MJ, Howlett-Smith H et al. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med 2005;352:1305-1316.
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Disclosure: The author reports no conflicts of interest.
We appreciate Dr. Cruz-Flores' comments and agree that the relevance of a composite criterion is certainly inferior to an individual end-point. In the GESICA study, the recurrence of ischemic events in the territory of a symptomatic intracranial stenosis defined the major end-point. [1] To what extent TIA and ischemic stroke (IS) are different entities and represent components of a composite end-point is unclear. They both constitute a recurrent cerebrovascular ischemic event, which is clearly different from a composite end-point including stroke and myocardial infarction.
TIA and IS share pathogenic mechanisms, and in this specific population of stroke patients (i.e., symptomatic intracranial stenosis), they are probably part of a continuum. The use of a conventional clinical definition for TIA (which does not include imaging) in the GESICA study suggests that a significant number of TIAs may have been classified as IS if the new definition of TIA is used. [6] TIAs are often a concern for patients and physicians and they are a serious condition which requires adequate therapeutic decisions. TIAs are an important determinant of stroke, with risks of stroke reported as high as 12% within the first month and looking back after an IS, 23% of patients do experience a TIA before their stroke, mainly in the preceding week. [3,7]
Currently, endovascular treatment remains under investigation. The initial high complications rates are decreasing as a result of interventionists' increasing experience and the development of dedicated devices. The most recent data report peri-procedural risks between 5.8% to 9.5% [8,9] and the long term follow-up available in patients treated with intracranial angioplasty or stenting shows annual stroke rates ranging between 3.2% to 7.1%. [1,9] These stroke rates constitute a better outcome compared to the 22%-stroke rate in the highest risk cohort in the WASID study. [2]
However, indications for endovascular intervention in patients with intracranial atherosclerotic remain to be established, but the identification of patients with the highest risk of recurrence of ischemic events will probably maximize the benefit/risk ratio of this technique.
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Disclosure: The authors report no conflicts of interest.