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Treatment Advances for Common Cause of Ischemic Stroke

Since Hippocrates first recognized stroke more than 2,400 years ago, its symptoms and causes have been well described. Yet, at least in the U.S., one potential contributing factor to the condition remains less studied, despite being the most common proximate mechanism of ischemic stroke worldwide: intracranial atherosclerotic disease (ICAD).

ICAD results from atherosclerosis of the large arteries at the base of the brain and is the third leading cause of stroke in the U.S., accounting for roughly 8% to 10% of cases (70,000) annually.

As ICAD is less widely known in this country, its treatment potential is often overlooked. Michael Alexander, MD, vice chair of Neurosurgery and director of the Neurovascular Center and Endovascular Neurosurgery at Cedars-Sinai, is a pioneer in stenting for ICAD and says improving how treatment modalities are promoted and shared with patients and physicians alike could have a direct correlation to positive long-term health outcomes.

“Dedicated stents for the brain emerged onto the scene in 2005, and clinical trials show very promising results in ICAD patients who failed medical therapy,” noted Alexander, who also heads Cedars-Sinai’s new ICAD Program. “But there is a lack of familiarity with the current literature, and patients and clinicians frequently aren’t aware of available treatment options.”

Groundbreaking trials

Medical therapies remain the first line of defense for patients with less than 70% blockage. When patients have a 70% or higher degree of blockage of one of the major arteries of the brain and have failed medical therapy, stenting the artery open is a valuable alternative for many of these patients. For patients who have a total artery blockage or smaller artery narrowing with a stroke, bypass surgery may be an option.

In 2019, Alexander and co-investigators published findings from the Wingspan Stent System Postmarket Surveillance (WEAVE) trial. Mandated by the FDA to assess the periprocedural safety of the Wingspan Stent System produced by Stryker Neurovascular, WEAVE enrolled 152 consecutive patients who met the FDA’s on-label usage criteria at 24 hospitals, where they underwent angioplasty and stenting with the Wingspan stent.

The trial demonstrated a lower-than-expected 2.6% periprocedural stroke, bleed and death rate and has subsequently become the benchmark for all future studies.

Alexander’s subsequent trial, WOVEN, was a long-term follow-up of the WEAVE cohort and confirmed a relatively low one-year stroke and death rate for stented patients.

In 2021, after publication of the trials, the American Stroke Association began recommending the procedure for ICAD patients who fail medical therapy. The trials also precipitated broader adoption of stenting as a viable treatment approach.

Analyzing the usage of stenting for ICAD in the National Inpatient Sample, Alexander found that stenting procedures have increased five-fold since 2014. He presented his data this past February at the American Heart Association’s International Stroke Conference in Dallas.

“This is obviously a therapy that is becoming more common in the U.S. and providing stroke patients with treatment alternatives,” he said. “Our trials gave neurointerventionalists the confidence to begin performing more of these procedures.”

Over the past three years, Alexander has lectured on the subject in 23 countries spanning six continents. Given his expertise and Cedars-Sinai’s position as No. 2 in the country for lowest stroke mortality rate (CMS Care Compare: All Hospitals), the Neurovascular Center is a national leader in stenting and surgery for ICAD.

Extending the golden hour

Unlike in the case of thrombectomy, ICAD does not require emergent treatment. Surgeons typically perform stenting procedures for ICAD within one to three weeks after a mild stroke or transient ischemic attack.

“We usually wait until a patient is more stable, which makes stenting a prime opportunity for referral to the best treatment center because there’s time to act and travel is a possibility,” Alexander said.

Prior to stenting, neurology specialists must first identify appropriate candidates. Alexander leverages high-resolution magnetic resonance angiography—Cedars-Sinai is at the forefront of innovations in this technology—to determine the cause of arterial blockage.

“We’re expert at finding people who fit the profile for treatments,” Alexander said.

That profile is likely to include patients between 40 and 70 years old who are experiencing arm weakness or difficulties with speech. In addition to age, risk factors include smoking, hypertension, diabetes, hyperlipidemia, obesity and family history. In the U.S., more ICAD patients are white, but the disease actually has a higher incidence among African Americans, Latinos and people of Asian descent.

“In some countries, such as China, ICAD is the leading cause of stroke—responsible for more than 45% of cases,” Alexander said.

Closer to home, Alexander notes that his caseload of ICAD patients is rapidly growing. “Neurologists and cardiologists from across the country are sending us patients because of our excellent reputation and outcomes,” he said. “We have a unique ability to help manage patients and prevent future strokes, and we’re proud to be advocates for treating this disease.”

Read Dr. Alexander’s comprehensive review of ICAD in Journal of NeuroInterventional SurgeryIntracranial Atherosclerosis Update for Neurointerventionalists.

If you’d like to refer a patient to Cedars-Sinai’s ICAD Program, please call 310-423-6587.


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