Level 1: Likely reliable evidence
Patients with a transient ischemic attack (TIA) or stroke due to intracranial arterial stenosis are at high risk of a subsequent stroke. Current recommendations from the American Heart Association and the American Stroke Association classify percutaneous transluminal angioplasty with stenting (PTAS) as an investigational intervention with unknown utility for these patients (Stroke. 2011;42:227-276). Nevertheless, PTAS is sometimes used in this clinical setting.
Another relatively new but not fully tested approach is aggressive medical management with dual antiplatelet therapy and intensive risk-factor management. The SAMMPRIS trial evaluated the addition of PTAS to aggressive medical management after a TIA or nondisabling stroke attributed to intracranial artery stenosis of 70%-90% (N Engl J Med. 2011; 365:993-1003). A total of 451 patients (mean age 60 years) were randomized within 30 days of ischemic event to PTAS plus aggressive medical management vs. aggressive medical management alone.
In the PTAS group, patients had the procedure within three business days of randomization. Most patients had clopidogrel 75 mg for at least five days prior to the procedure. Those who did not were given a loading dose of clopidogrel 600 mg at six to 24 hours before surgery. All patients received aggressive medical management, which included aspirin 325 mg and clopidogrel 75 mg daily for 90 days in addition to medical and lifestyle interventions to improve primary and secondary risk factors (including blood pressure, cholesterol levels, diabetes, smoking, weight and exercise).
The primary endpoint was a composite of ischemic stroke or death within 30 days of enrollment or a revascularization procedure or stroke in the territory of a qualifying artery at any time beyond 30 days. PTAS significantly increased the risk of this outcome (20.5% vs.11.5, P=0.009, NNH=12). Within the first 30 days, ischemic stroke or death occurred in 14.7% of the PTAS group vs. 5.8% of controls (P=0.002, NNH=11).
PTAS was also associated with increased risk of stroke at any time during follow-up (22.3% vs. 14.1%, P=0.03, NNH=12) and increased risk of major hemorrhages requiring intervention (9.8% vs. 2.2%, P<0.001, NNH=13). There was no significant difference in overall mortality (3.1% vs. 3.1%).
After mean follow-up of 11.9 months, enrollment was terminated due to safety concerns and futility analyses indicating there was minimal chance that PTAS would show benefits by the end of the planned two-year follow-up period.