Medical Therapy Alone Superior to Stenting for Intracranial Stenosis

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For symptomatic patients with severe intracranial stenosis, aggressive medical management alone reduces the risk of periprocedural stroke and death compared with stenting, and at midterm follow-up provides similar protection against recurrent stroke. The findings were published online September 7, 2011, ahead of print in the New England Journal of Medicine.

For the SAMMPRIS (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial, investigators led by Marc I. Chimowitz, MB, ChB, of the Medical University of South Carolina, Charleston (Charleston, SC), studied 451 patients with a recent transient ischemic attack (TIA) or stroke due to significant stenosis (70%-99%) of a major intracranial artery. Patients were randomized to aggressive medical therapy with (n = 224) or without (n = 227) stenting.

Medical therapy consisted of dual antiplatelet therapy and intensive management of primary and secondary risk factors; angioplasty was performed with the Gateway PTA Balloon Catheter and the self-expanding Wingspan stent (both Stryker Neurovascular; Kalamazoo, MI).

The 2 treatment groups had similar baseline characteristics, although at various times during follow-up they differed with regard to certain risk factors. In the group assigned to stenting, 6.7% in fact did not receive a stent, whereas in the group assigned to medical management alone, 4.0% underwent stenting after a TIA.

Early Termination

Trial enrollment was terminated early on the recommendation of the data and safety monitoring board due to safety concerns in the stenting group and because futility analyses indicated that there was virtually no chance that stenting would show a benefit by the end of planned follow-up.

Stroke or death within 30 days occurred more than twice as often among stented patients as among those receiving medical therapy alone. The rate of any stroke was also higher in the stented group. In addition, there were 5 stroke-related deaths in the stented group compared with 1 non-stroke-related death in the medical management group (table 1).

Table 1. Major Adverse Events at 30 Days

 

Medical Management
(
n = 227)

Stenting
(n = 224)

P Value

Stroke or Death

5.8%

14.7%

0.002

Death

0.4%

2.2%

0.95

Any Stroke

5.3%

14.7%

0.03

 

Beyond 30 days, 13 patients in each group experienced a nonfatal ischemic stroke in the territory of the qualifying artery. At 1 year, adverse outcomes continued to be elevated in the stenting arm (table 2).

 Table 2. Major Adverse Events at 1 Year

 

Medical Management
(n = 227)

Stenting
(n = 224)

P Value

Any Stroke

14.9%

22.3%

0.03

Major Hemorrhage

1.8%

9.0%

< 0.001

Any Stroke or Death

17.5%

23.4%

0.06

 

The difference between the treatment groups was driven by early events; beyond 30 days, stroke rates were similar. However, because fewer than half the patients were followed for longer than 1 year, continued follow-up will be important to determine the long-term outcomes for the 2 strategies, Dr. Chimowitz and colleagues say.

Poor Stenting Results a Surprise

According to the authors, the incidence of periprocedural stroke or death after stenting was substantially higher than reported in a phase 1 trial or previous registries. The discrepancy is not attributable to differences in the quality of the operators, they say, since all were experienced and in fact had also been involved in the earlier studies.

The researchers do offer potential explanations. For one, patients in the current trial had more severe stenoses and recent symptoms. The latter is a marker of unstable plaque, which could increase the risk of distal embolism. Another possibility is that the trial’s rigorous neurological assessment may have detected more mild strokes.

Michael J. Alexander, MD, of Cedars-Sinai Medical Center (Los Angeles, CA), who was involved in early testing of the Wingspan stent, similarly pointed to features of the trial that may have contributed to unfavorable results for stenting. In a press release, he noted that:

  • Sicker patients, such as those with multiple or long stenoses, were excluded—yet they are most likely to benefit from stenting
  • Most patients had blockages in smaller arteries, which are difficult to treat with stenting

On the other hand, the stroke rate in the medical management group was much lower than expected, according to Dr. Chimowitz and colleagues. They express surprise at the extent and rapidity of that reduction, adding that combined use of aspirin and clopidogrel may also have contributed to early safety by reducing the likelihood of distal microemboli.

Intracranial Stenting Challenging

In an accompanying editorial, Joseph P. Broderick, MD, of the University of Cincinnati College of Medicine (Cincinnati, OH), notes that SAMMPRIS is the third randomized trial of intracranial revascularization to show negative results—2 earlier trials of intracranial-extracranial bypass surgery also failed to find an advantage for stroke prevention compared with medical therapy.

Moreover, not only was the rate of periprocedural stroke or death associated with stenting quite high in the current trial, but surprisingly one-third of all strokes consisted of symptomatic hemorrhagic events, a relatively rare complication of carotid stenting, Dr. Broderick writes. This finding underlines the fact that intracranial stenting is technically more challenging than extracranial carotid stenting due to the tortuosity of the internal carotid artery, he observes.

Dr. Broderick also points out that aggressive medical management, and possibly the short-term addition of clopidogrel to aspirin, yielded unexpectedly low 1-year rates of recurrent stroke, while subsequent ischemic strokes in the same arterial territory were evenly distributed between the 2 treatment arms. “These observations raise the question of whether current aggressive management of risk factors may be equivalent or superior to stenting or carotid endarterectomy in patients with asymptomatic extracranial carotid stenosis,” he writes.

A Niche for Stenting?

Meanwhile, Society for Cardiovascular Angiography and Interventions president Christopher J. White, MD, of the John Ochsner Heart and Vascular Institute (New Orleans, LA), suggested that medical therapy may not be the answer for everyone. “A continuing concern is what to do for patients who have failed medical therapy, or have recurrent symptoms (TIAs or strokes) while receiving medical therapy,” he noted in an e-mail communication with TCTMD.  “This high-risk group continues to look for an answer with revascularization.”

Dr. White added that, judging from the trial results, the self-expanding Wingspan stent may not be the best device for intracranial intervention.

 

Sources:

  1. Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011;Epub ahead of print.
  2. Broderick JP. The challenges of intracranial revascularization for stroke prevention. N Engl J Med. 2011;Epub ahead of print.

 

Related Stories:

  1. New Research Expands Understanding of Cerebrovascular Stents
  2. Carotid Stenting Linked to More Intracranial Hemorrhages Than Endarterectomy
Disclosures
  • The SAMMPRIS trial was supported by a research grant from the National Institute of Neurological Disorders and Stroke and research support from AstraZeneca, Nationwide Better Health-INTERVENT, and Stryker Neurovascular.
  • Dr. Chimowitz reports no relevant conflicts of interest.
  • Dr. Broderick reports receiving consulting fees from Genentech.
  • Dr. Alexander reports serving as a consultant and proctor for Stryker Neurovascular.
  • Dr. White reports having served as principal investigator of the CABANA study, which was sponsored by Boston Scientific.

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