After Stroke & TIA: Medical Management vs Angioplasty and Stenting

Dr. Colin Derdeyn Mallinckrodt Institute of Radiology and the Departments of Neurology and Neurosurgery Washington University School of Medicine, St Louis, MO, Interview with:
Dr. Colin Derdeyn
Mallinckrodt Institute of Radiology and the Departments of Neurology and Neurosurgery
Washington University School of Medicine, St Louis, MO, USA What are the main findings of the study? 

Dr. Derdeyn: The primary results indicate that medical management, consisting of dual antiplatelets for 3 months after a transient ischemic attack (TIA) or stroke, and rapid, effective control of blood pressure (systolic BP less than 140 mm Hg and 130 mm Hg if diabetic) and LDL-cholesterol (less than 70 mg/dl), in addition to management of other risk factors, is superior to angioplasty and stenting in addition to the same medical regimen for reducing the risk of future stroke in patients with severe atherosclerotic stenosis (>70%) of a major intracranial artery.    In addition, while there were subgroups at higher risk for stroke on medical treatment (older age, female gender, prior stroke in the territory),  none of these subgroups appeared to have a benefit from stenting (i.e. stroke rates in the stenting groups in these subgroups was higher too). 
Were any of the findings unexpected?

Dr. Derdeyn:  Yes.  The dramatic and unexpectedly low rate of recurrent stroke in the medical group that was observed in the analysis of the early results (complete 30-day outcomes and outcome to one year in half the enrolled patients) persisted during the extended follow up.  In the present study, we completed 2 year follow up in all enrolled subjects, and follow up to 4 years in some.  The median follow up was 32 months.  The risk of stroke at one year in the medical group was 12% and 14% at two years.  We had expected a 25% risk of stroke in the medical group at two years, based on prior prospective longitudinal studies of medical treatment in this same population.   We attribute this unexpected apparent benefit to the efficacy of the aggressive medical regimen – dual antiplatelets and risk factor reduction.

The other surprise was the lack of any apparent late gain in the stenting group.  The risk of stroke after 1 year in both the stenting and the medical groups were nearly identical.   We expected after the initial 30-day period where the intervention group was at risk of procedural complications,  the benefit of angioplasty and stenting the underlying stenosis would start to show up.   We expected the medical group would have a higher risk of stroke than the stenting group after the post-operative period.   This did not happen at all.   It again points to the unexpected and powerful impact of risk factor reduction in this particularly high-risk population.  It suggests that despite the presence of severe narrowing of a major brain artery, the pathogenesis of recurrent stroke in this population is amenable to medical intervention in most patients.  This is really interesting.

We also closely examined subgroups at that might be at high risk for future stroke on medical therapy (pre-specified).  None of the subgroups showed a trend suggesting possible benefit for stenting.  One interesting and unexpected, and grossly under-powered, finding was the relatively low risk of stroke on medical therapy for patients with stenoses of the vertebral and basilar arteries.  These locations had been thought to carry the highest risk of stroke on medical therapy.  In addition, based on our prior analyses of SAMMPRIS data and procedural complications,  these locations had the highest risks for procedural stroke.  This was related to occlusion of perforators on these vessel segments. What should clinicians and patients take away from your report? 

Dr. Derdeyn: Patients with TIA or stroke related to a severe stenosis of an intracranial artery should be treated with a SAMMPRIS-like medical regimen, with close attention paid to bringing LDL-cholesterol and systolic blood pressure into guideline-recommended levels.  Angioplasty and stenting may still have some role in very uncommon situations not addressed in this study.  For example, some rare patients present with orthostatic symptoms that do not respond to medical management and stenting may be reasonable in these patients. What recommendations do you have for future research as a result of this study?

Dr. Derdeyn: We are still digesting all the final data and anticipate several future publications exploring different aspects of the medical management more fully.   In addition, we want to better characterize the lesions angiographically to look for clues on relationship with outcomes.  The findings from these analyses will have some impact on the future directions.

That said,  there are two major future directions.

First, we need to identify the mechanism of stroke in these patients (embolic, hemodynamic) and determine if we can identify high risk groups.   For example,  trials of intervention for carotid stenosis in the neck showed benefit in groups selected only by degree of stenosis and presence of ischemic symptoms.   That clearly didn’t work in the head, and we need to drill deeper into mechanism to find high risk groups that may benefit from targeted medical or interventional intervention.   There are a lot of candidate methods to do this in longitudinal studies – high resolution MR looking at plaque biology (embolic potential), measurements of hemodynamic impairment.

The second direction is to investigate different methods of angioplasty and or stenting.  Complications from the procedure may be reduced with different devices.  Angioplasty alone, without stenting, is one approach that needs to be prospectively tested.  Testing this will only be ethical if we can identify a high risk group.  We have some clues for what this group may be from SAMMPRIS.


Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial
Prof Colin P Derdeyn MD,Prof Marc I Chimowitz MBChB,Michael J Lynn MS,Prof David Fiorella MD,Tanya N Turan MD,L Scott Janis PhD,Jean Montgomery RN,Azhar Nizam MS,Bethany F Lane RN,Prof Helmi L Lutsep MD,Stanley L Barnwell MD,Michael F Waters MD,Brian L Hoh MD,J Maurice Hourihane MD,Prof Elad I Levy MD,Prof Andrei V Alexandrov MD,Mark R Harrigan MD,Prof David Chiu MD,Richard P Klucznik MD,Joni M Clark MD,Prof Cameron G McDougall MD,Mark D Johnson MD,G Lee Pride MD,John R Lynch MD,Prof Osama O Zaidat MD,Prof Zoran Rumboldt MD,Prof Harry J Cloft MD,for the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Trial Investigators
The Lancet – 26 October 2013
DOI: 10.1016/S0140-6736(13)62038-3

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