Long-term outcomes of a randomized clinical trial of stenting vs aggressive medical therapy for intracranial arterial stenosis. Neurosurgery 2014

Starke RM, Komotar RJ, Connolly ES. Long-term outcomes of a randomized clinical trial of stenting vs aggressive medical therapy for intracranial arterial stenosis. Neurosurgery 2014;75:N19-21.

Stroke is a leading cause of morbidity and mortality and the most significant source of disability in the United States. Recent trials have demonstrated that although outcomes for stroke patients are improving with aggressive medical therapy, the overall long term prognosis is poor. In the initial stenting and aggressive medical management for preventing recurrent stroke in intracranial stenosis (SAMMPRIS) trial, patients with a recent transient ischemic attack or stroke attributed to stenosis of 70–99% of the diameter of a major intracranial artery were randomized to aggressive medical management alone or aggressive medical management plus percutaneous transluminal angioplasty and stenting (PTAS) using Wingspan stent system.[1] Aggressive medical management included antiplatelet therapy, intensive management of vascular risk factors and lifestyle modification program. The primary end point was stroke or death within 30 days after enrollment or after a revascularization procedure for the qualifying lesion during the follow-up period or stroke in the territory of the qualifying artery beyond 30 days. Enrollment was stopped after 451 patients underwent randomization because 30 days stroke rate or death was 5.8% in the medical cohort compared with 14.7% in the PTAS cohort.

The final results showed that during a median follow-up of 32.4 months, the primary end point was significantly higher in those receiving PTAS (23%) compared with those receiving aggressive medical therapy alone (15%). Beyond 30 days, 10% of patients in each group had a primary end point. The occurrence of any stroke was higher in the PTAS group (26%) compared with medical cohort (19%), and major hemorrhage was seen in 13% of those in PTAS group versus 4% in the medical management cohort.[2] Compared with Warfarin-Aspirin Symptomatic Intracranial Disease Trial,[3] the stroke rates were much lower in the SAMMPRIS medical cohort. It could be because in the former, patients were treated with risk factor management and either warfarin or aspirin while in latter, patients were treated with aggressive risk factor management along with aspirin and clopidogrel for 90 days followed by aspirin alone. The number of patients attaining blood pressure and low-density lipoprotein control was much higher in SAMMPRIS trial and concerns have been raised that aggressive medical therapy in SAMMPRIS does not reflect current practice and can explain the significantly higher number of patients lost to follow-up.

It is unclear about the number of patients in the interventional cohort who had significant in-stent stenosis or thrombosis. In Wingspan stent the rate may be >30%.[4] However, it is the only stent approved by US Food and Drug Administration for use in patients with atherosclerotic intracranial arterial stenosis. The limitations of the stent include the necessity of angioplasty with a separate balloon before stent deployment followed by a microwire exchange for stent placement. The patients with intracranial arterial stenosis experiencing repeated strokes after initiation of best medical therapy suggest it to be beneficial alternative. It may be a favorable therapeutic option in patients who could not achieve the goals of best medical therapy, including blood pressure, low-density lipoprotein, and diabetes control along with weight reduction and exercise.

No conflict of interest has been declared by the author(s).

• REFERENCES

• 1 Chimowitz MI, Lynn MJ, Derdeyn CP, Turan TN, Fiorella D, Lane BF. et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med 2011; 365: 993-1003
• 2 Derdeyn CP, Chimowitz MI, Lynn MJ, Fiorella D, Turan TN, Janis LS. et al. Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial. Lancet 2014; 383: 333-41
• 3 Chimowitz MI, Lynn MJ, Howlett-Smith H, Stern BJ, Hertzberg VS, Frankel MR. et al. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med 2005; 352: 1305-16
• 4 Ding D, Starke RM, Crowley RW, Liu KC. Role of stenting for intracranial atherosclerosis in the post-SAMMPRIS era. Biomed Res Int 2013; 2013: 304320