The Triumph of Tablets

Published - Written by Lisa Rosenbaum

In this week’s NEJM, tablets once again trump technology in the treatment of obstructive atherosclerosis; this time in the brain.

Many of the advances in the treatment of ischemic stroke have followed on the heels of similar advances in the treatment of ischemic coronary disease. From thrombolysis in acute stroke, to stenting for symptomatic extracranial carotid disease, revascularization has shown clear benefit. However, as the 2007 COURAGE trial showed, surprisingly, aggressive medical therapy is as effective as revascularization for stable coronary disease. And now, we take this somewhat counterintuitive finding one step further, into the treatment of acute stroke.

Chimowitz et al. demonstrate the superiority of aggressive medical therapy to percutaneous revascularization for intracranial carotid disease.  And medicines ruled. So much so, in fact, that the trial was stopped early because the rate of death or stroke was 14.7% in the group receiving stents, versus 5.8% in the group treated with antiplatelet agents plus aggressive management of risk factors.

This trial, known as SAMMPRIS, (Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis), randomized patients who had a 70-99% intracranial stenosis, and had had a TIA or nondisabling stroke within 30 days of enrollment. Patients were randomized to medical therapy alone, or medical therapy in addition to percutaneous transluminal angioplasty and stenting (PTAS). Medical treatment consisted of aspirin 325 mg, clopidogrel 75 mg, as well as aggressive management of risk factors, including blood pressure, lipids, and diabetes. PTAS was performed by experienced neurointerventionalists screened and pre-selected for the purposes of the study.

The primary endpoint was stroke or death within 30 days of enrollment or within 30 days of a revascularization procedure during follow-up. The primary endpoint also included stroke within the territory of the culprit artery beyond 30 days.  The primary endpoint was about 2.5 times higher in the patients randomized to PTAS than in those treated with medical therapy alone. Also of note, of the 33 strokes that occurred within 30 days in the PTAS group, 25 occurred within one day of the procedure, and 8 occurred within 2-6 days. These results likely speak to the technical difficulty of intracranial revascularization as compared to extracranial revascularization. The results also firmly emphasize that the safety of a device for one purpose does not necessarily translate into the safety and efficacy of that same device for another. Hence, the importance of clinical trials.

Though it is always somewhat disappointing to receive the results of a negative trial, especially given the high morbidity and mortality associated with stroke, there is indeed a silver lining. Tablets. The authors note that approximately 23% of patients with high-grade stensoses who have had TIA or stroke have another within one year. But in SAMMPRIS the rate of stroke with aggressive medical therapy, including 90 days of clopidogrel, was far lower, at 5.8%. Medicines may not pack the visual punch of a wide- open artery, but once again, the tablet triumphs.