Medical management superior to stenting for stroke related to intracranial arterial stenosis [Classics Series]

1. The risk of early stroke after angioplasty and stenting of intracranial atherosclerotic lesions was higher than expected, while the risk of stroke with aggressive medical therapy alone was lower than expected.

2. The probability of ischemic stroke, symptomatic brain hemorrhage, and non-stroke related death after stenting plus medical management was significantly greater than medical management alone.

Original Date of Publication: September 2011

This study summary is an excerpt from the book 2 Minute Medicine’s The Classics in Medicine: Summaries of the Landmark Trials, 2e (The Classics Series).

Study Rundown: Atherosclerotic intracranial arterial stenosis is an important cause of ischemic stroke and a major predictor of recurrent stroke following an initial event. Combination antiplatelet therapy and risk factor management have long been regarded as mainstays in the treatment and prevention of recurrent stroke. However, with the approval of the first self-expanding nitinol stent by the Food and Drug Administration (FDA) in 2005 for use in patients with atherosclerotic intracranial arterial stenosis, percutaneous transluminal angioplasty and stenting (PTAS) in addition to antithrombotic therapy emerged as a potential alternative approach towards the treatment of high-risk patients.

In the randomized controlled trial conducted by Chimowitz and colleagues, the safety and efficacy of PTAS and medical therapy was compared to medical therapy alone in high-risk patients with intracranial arterial stenosis. The results of this trial showed that aggressive medical management alone was superior to PTAS plus medical management, demonstrating a lower risk of recurrent ischemic stroke.

Please click to read study in NEJM

In-Depth [randomized controlled trial]: This study was conducted in 50 sites across the United States. To be considered eligible for participation in the study, patients must have experienced a transient ischemic attack (TIA) or nondisabling stroke within 30 days of enrollment, attributed to intracranial arterial stenosis of 70-99% of a major intracranial artery. Arterial stenosis was verified angiographically. Patients with tandem extracranial or intracranial stenosis, an occlusion located proximally or distally to the target intracranial lesion, or bilateral intracranial vertebral artery stenosis were excluded. Following screening and consent, patients were randomized to receive PTAS and medical management or medical management alone. Medical therapy consisted of aspirin 325 mg daily throughout follow-up and clopidogrel 75 mg daily for 90 days after enrollment, as well as management of primary (elevated systolic blood pressure and low-density lipoprotein (LDL) cholesterol levels) and secondary risk factors (diabetes, elevated non-high-density lipoprotein (non-HDL) cholesterol levels, smoking, excess weight and sedentarism) through a lifestyle modification program. Primary endpoints of the study included ischemic stroke, symptomatic brain hemorrhage, and non-stroke related death within 30 days after enrollment, as well as ischemic stroke in the territory of the qualifying lesion beyond 30 days of enrollment.

A total of 451 patients were randomized to receive either PTAS and medical therapy (n = 224; mean age 61.0 years, SD 10.7; 56.7% male) or medical therapy alone (n = 227; mean age 59.5 years, SD 11.8 years; 63.9% male). There were no significant differences between the groups with respect to baseline patient characteristics. In the PTAS group, the probability of experiencing any primary end point within 30 days after enrollment was considerably higher at 14.7% compared to 5.8% in the medical management group (p = 0.002). In addition, while no patients in the medical management group experienced symptomatic brain hemorrhage during the 30-day follow-up period, 10 of the 33 strokes (30.3%) in the PTAS group resulted in this outcome (p = 0.04). Over 1 year of follow-up, the probability of experiencing a primary endpoint was also significantly greater in the PTAS group (20.2%) compared to the medical management group (12.2%) (p = 0.009).

Chimowitz MI, Lynn MJ, Derdeyn CP, Turan TN, Fiorella D, Lane BF, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. The New England Journal of Medicine. 2011 Sep;365(11):993-1003.

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