Fiorella: Promising treatment for strokes

Dr. David Fiorella is professor of clinical neurological surgery and radiology at Stony Brook University School of Medicine. He is one of the national co-principal investigators of SAMMPRIS, and one of the lead authors of the NEJM paper.

It's imperative for researchers to identify, test and advance therapies for the treatment and prevention of stroke. Stroke is the leading cause of disability and the third-leading cause of death in the United States, with approximately 800,000 occurrences and 144,000 deaths annually.

One treatment, the Wingspan Stent System, became available in 2005, when the Food and Drug Administration approved it under "humanitarian device exemption" for certain patients with symptomatic blockages of their brain arteries at high risk for stroke. The Wingspan stent, a tiny, flexible, mesh-like tube, is placed into narrowed blood vessels in the brain to prop them open and improve blood flow.

The exemption facilitates the approval of devices designed to treat relatively small numbers of patients with severe diseases who lack good treatment options. It requires that studies show "safety and probable benefit," rather than the more extensive process required for premarket approval. Wingspan approval was achieved without a randomized clinical trial, and since then, physicians have been using the device to treat qualifying patients within the context of routine clinical care.

Since there was little clinical evidence available to guide the selection of patients for stenting with Wingspan, Marc Chimowitz of the Medical University of South Carolina, Charleston, Dr. Colin Derdeyn of Washington University School of Medicine in St. Louis and I proposed the first randomized, multicenter clinical trial to compare medical therapy to stenting. With the approval of the FDA and funding from the National Institutes of Health, we designed and led the SAMMPRIS trial -- stenting versus aggressive medical management for preventing recurrent stroke in intracranial stenosis -- which compared stenting to aggressive drug treatment head-to-head in 451 patients at 50 stroke centers nationwide.

Our study made headlines earlier this month when it was halted due to the clear superiority of the medication approach over stenting. This was an unexpected and significant finding, so the results received nationwide media attention. The headline "EXPERIMENT'S OVER" ran in Newsday on Sept. 14, on a story that, unfortunately, left the impression that the trial was a failure because stenting did not "win." Nothing could be further from the truth.

The trial results, recently published in The New England Journal of Medicine, revealed that patients who had aggressive medical therapy alone -- without stents -- had a greatly reduced risk of second stroke and death: 12.2 percent over one year, less than half of the 25 percent rate expected with standard medical therapy. This aggressive medical management, which was designed specifically for the SAMMPRIS trial, consisted of early treatment with two platelet-blocking agents as well as medications to significantly lower cholesterol levels and control high blood pressure. In addition to being more effective, it is considerably less expensive than stenting.

By contrast, patients receiving stents experienced a second stroke or died within one year about 20 percent of the time, comparable to the 25 percent rate expected with standard medical therapy -- but clearly inferior to the 12.2 percent associated with the new medical management protocol.

These findings provide solid evidence that will fundamentally guide the treatment of high-risk stroke patients in the future. Ultimately, the study will benefit many thousands of patients at risk for stroke worldwide, saving lives and improving quality of life.

Participating institutions, their investigators and their patients should be congratulated for taking part in this study. NIH-supported, well-designed, and rigorously supervised, randomized clinical trials like SAMMPRIS represent the best of both clinical and academic medicine. More important, these efforts are essential to establishing new therapies, evaluating existing treatments and defining optimal care for our patients. In SAMMPRIS, we sought to improve the existing standard of treatment for patients with intracranial atherosclerosis and the results proved that we did.