Dive Brief:

• FDA on Thursday alerted neurointerventionalists to postmarket data from Stryker indicating heightened risk of stroke and death among patients receiving the company's Wingspan stent system for off-label indications.
• The device is used to open narrowed arteries of patients diagnosed with intracranial stenosis who experience repeated strokes, a life-threatening condition with few treatment options, FDA said. Wingspan was originally approved through the Humanitarian Device Exemption pathway in 2005.
• In 2012, following a labeling revision and safety communication to healthcare providers, FDA issued Stryker a 522 postmarket study order. Results from that 198-patient Wingspan Stent System Postmarket Surveillance (WEAVE) study indicated off-label use "significantly increases the risk of stroke or death," FDA warned.

Dive Insight:

When plaque buildup narrows arteries in the brain, blood flow to the brain can be reduced, increasing risk for stroke. The potentially life-threatening condition is known as intracranial stenosis or intracranial atherosclerotic disease.

Stryker's Wingspan stent system has aimed to serve that patient group, but a high incidence of stroke and death among those treated with the product had led FDA to further refine the device's indicated population since 2005. Still, off-label use of the device has persisted, pushing the agency to the new alert.

"This benefit risk paradigm can shift when a device intended for a specific patient population is used in other ways," said William Maisel, chief medical officer in FDA’s device center, in a statement. "While the device can play an important role in opening narrowed arteries in the brain of certain patients diagnosed with intracranial stenosis who are experiencing repeated strokes, new study data issued today reinforces that the risk of stroke or death is higher when this device is used in patient populations outside of the FDA-approved indications for use."

One former FDA official critical of the initial approval of the Stryker device applauded the move.

"This safety communication is about a problem that is not uncommon with medical devices," Larry Kessler, former director of the Office of Surveillance and Biometrics at FDA's Center for Devices and Radiological Health, told MedTech Dive.

"The safety profile or product being used off label is often either weak or sometimes even non-existent. This is a really excellent safety communication because it shows with limited data there's a potential for more serious adverse events for this particular product," he added.

But the consumer advocacy group Public Citizen, which called for a government-mandated recall of the product in 2011, is not assuaged.

FDA had convened an advisory committee meeting on the device and subsequently issued a safety communication in 2012. The agency said panelists agreed the Wingspan device remained an important treatment option for certain patients, but that evidence was lacking that the Wingspan device provided superior benefits in most patients with the condition when compared to alternative aggressive medical therapy.

Sidney Wolfe, co-founder of Public Citizen's Health Research Group, told MedTech Dive he still believes FDA should have taken the product off the market. He argues the safety profile of the approved indication for Stryker's stent still does not show a unique benefit compared to medication.

"You can't have off-label use of a product that isn't on the market, that's the best way of stopping the off-label use," Wolfe said. 

FDA said it worked with Stryker in 2012 to refine indications and update labeling, with Stryker initiating the prospective, single arm, 24-center WEAVE study shortly after to measure rates of stroke and death within 72 hours of stent placement. Of 198 patients studied, 152 fell within the indicated treatment population, while 46 received off-label use.

While four individuals, or 2.6% of the on-label recipient group, experienced stroke or death, incidence rose to 23.9% among the off-label group, or 11 patients.

FDA made clear the device is only indicated for patients:

• who are between the ages of 22 and 80 years old who have had two or more strokes despite aggressive medical management;
• whose most recent stroke occurred more than seven days prior to planned treatment with Wingspan;
• who have 70-99 percent stenosis due to atherosclerosis of the intracranial artery related to the recurrent strokes; and who have made good recovery from the previous stroke and have a modified Rankin Scale score, which measures degree of disability at time of evaluation on a regressive scale, of three or less prior to Wingspan treatment.