New Horizons in Stroke Prevention for Intracranial Atherosclerosis

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This article presents a concise and expert-validated summary of the guidelines from "Stroke Prevention in Symptomatic Large Artery Intracranial Atherosclerosis Practice Advisory," published in 2022 in Neurology (Turan TN et al., American Academy of Neurology). The document was developed by a multinational team of leading neurologists, neurosurgeons, clinical researchers, and vascular specialists from the U.S. and Europe, including Professor Tanya Turan (Medical University of South Carolina), Dr. Osama Zaidat (Mercy Health, Toledo), Professor Marc Chimowitz (Medical University of South Carolina), Dr. Larry Goldstein (University of Kentucky), Dr. Nestor Gonzalez (Cedars-Sinai Medical Center), and others. The guidelines have been approved by the Clinical Practice Guidelines Subcommittee of the American Academy of Neurology (AAN).

In the sections below, you'll find the most essential information patients and their families need to know about symptomatic intracranial atherosclerotic stenosis (sICAS), based on the latest scientific recommendations and results from the largest clinical trials in the field.

“Symptomatic intracranial atherosclerotic stenosis requires a comprehensive approach: strict control of risk factors, personalized treatment, and informed patient participation are key to reducing the risk of recurrent stroke.”

Expert Insights

Symptomatic intracranial atherosclerotic stenosis (sICAS) is one of the most common causes of ischemic stroke globally and is associated with a high risk of recurrent stroke or death. Over the past decades, clinical practice has evolved thanks to large-scale studies and meta-analyses that have identified which therapies and strategies are most effective in reducing this risk. Below are five key expert opinions and scientific recommendations that summarize current best practices for managing patients with sICAS. Each point is supported by direct quotes from the official American Academy of Neurology (AAN) guideline, with explanations about their significance for patients and families.

1. What is the most recommended long-term medication strategy for preventing stroke in sICAS?

Expert Opinion:

“Clinicians should recommend aspirin 325 mg/d for long-term prevention of stroke and death and should recommend adding clopidogrel 75 mg/d to aspirin for up to 90 days to further reduce stroke risk in patients with severe (70%–99%) sICAS who have low risk of hemorrhagic transformation.”

Explanation: Aspirin (325 mg/day) is the foundational long-term therapy for preventing stroke and death in patients with sICAS. In cases of severe stenosis (70–99%), clopidogrel (75 mg/day) is added to aspirin for up to 90 days, provided the risk of hemorrhagic transformation is low. This combination has shown the best balance of effectiveness and safety in clinical trials to date.

2. What is the role and goal of statin therapy for these patients?

Expert Opinion:

“Clinicians should recommend high-intensity statin therapy to achieve a goal low-density lipoprotein cholesterol level <70 mg/dL in patients with sICAS to reduce the risk of recurrent stroke and vascular events (Level B).”

Explanation: High-intensity statin therapy aimed at lowering LDL cholesterol to below 70 mg/dL is strongly recommended. Patients with sICAS face a greater risk of vascular events, and achieving low LDL levels significantly reduces that risk. In addition, blood pressure control to below 140/90 mmHg is essential (Recommendation 6).

3. Should endovascular and surgical interventions be used to prevent stroke?

Expert Opinion:

“Clinicians should not recommend percutaneous transluminal angioplasty and stenting for stroke prevention in patients with moderate (50%–69%) sICAS or as the initial treatment for stroke prevention in patients with severe sICAS. Clinicians should not routinely recommend angioplasty alone or indirect bypass for stroke prevention in patients with sICAS outside clinical trials. Clinicians should not recommend direct bypass for stroke prevention in patients with sICAS.”

Explanation: Previously common procedures like stenting, angioplasty, or surgical bypass have not shown benefits and carry higher complication risks compared to optimal medical therapy. These procedures are only recommended within clinical trials.

4. What additional lifestyle changes are recommended for patients with sICAS?

Expert Opinion:

“Clinicians should recommend at least moderate physical activity in patients with sICAS who are safely capable of exercise to reduce the risk of recurrent stroke and vascular events (Level B). ... Clinicians must recommend treatment of other modifiable vascular risk factors in patients with sICAS to reduce the risk of recurrent stroke and vascular events (Level A).”

Explanation: Moderate physical activity (at least 3–5 times per week) significantly reduces the risk of recurrent stroke. Controlling other vascular risk factors—such as diabetes, smoking, obesity, and high cholesterol—is crucial for secondary prevention.

5. What are the main risk factors for recurrent stroke in sICAS, and how can they be managed?

Expert Opinion:

“Among patients with sICAS, a post hoc analysis of SAMMPRIS showed that not performing moderate physical activity at least 3–5 times per week was associated with a higher risk of recurrent stroke and vascular events (OR 6.7, 95% CI 2.5–18.1). ... For patients with severe (70%–99%) sICAS, not controlling systolic blood pressure (SBP) and LDL cholesterol to recommended targets were associated with increased risk.”

Explanation: The primary risk factors for recurrent stroke include uncontrolled blood pressure, high cholesterol levels, low physical activity, diabetes, and severe stenosis. Patients must be diligent in managing these risks to reduce the chances of another stroke.

Q&A

1. How common is this condition globally, and does race or ethnicity matter?

Answer: sICAS is one of the leading causes of stroke worldwide and is particularly common among Asian, Black, and Hispanic populations. Its prevalence increases with age and demographic shifts:

"The global burden of stroke associated with sICAS is expected to rise as the population ages and as Asian, Black, and Hispanic populations, which have a higher prevalence of sICAS, increase..."

2. How is sICAS diagnosed? Is there a "gold standard"?

Answer: There is no single universally recognized "gold standard" for diagnosis. Multiple methods are used, each with varying sensitivity and specificity: magnetic resonance angiography (MRA), CT angiography, transcranial Doppler, and conventional (invasive) cerebral angiography:

“There is no diagnostic gold standard for diagnosing sICAS and various noninvasive and invasive techniques (e.g., magnetic resonance angiography, CT angiography, transcranial Doppler, and catheter cerebral angiography) are used with varying sensitivity and specificity.”

3. Can we predict who is at higher risk of having another stroke?

Answer: Yes, several modifiable and non-modifiable risk factors increase the chance of recurrence. Key ones include uncontrolled blood pressure, high cholesterol, low physical activity, diabetes, more severe stenosis, and some specific findings on imaging (such as "low distal flow status"). For example:

"Strict BP control plus low distal flow status — 6.2 (Low confidence)" "Physical activity (out of target) — 6.7 (High confidence)"

4. Does it matter if I've had a recent stroke, and how does that affect my risk?

Answer: Yes, the risk of another stroke is highest in the days and weeks following the initial event. That’s why prompt evaluation and starting preventive treatment quickly are especially important:

“Expeditious evaluation is reasonable as the highest risk of recurrent stroke is soon after the incident event.”

5. Could treatment carry risks, and what side effects should I watch for?

Answer: Some medications, especially anticoagulants like warfarin, increase the risk of serious bleeding and death without offering better stroke protection than aspirin. For example:

"For patients with sICAS, it is likely that warfarin, as compared with aspirin, increases the risk of major hemorrhage (RD 5.1%, 95% CI 1.2%–9.1%) and death (RD 5.4%, 95% CI 1.2%–9.8%)."

Conclusion

In conclusion, the expert guidance from the American Academy of Neurology (AAN), developed by leading specialists and published in Neurology, makes it clear that symptomatic intracranial atherosclerotic stenosis requires a comprehensive and individualized approach. Accurate diagnosis, careful risk assessment, strict management of key vascular risk factors, and informed patient involvement in treatment decisions are all critical to successful prevention and long-term health. These science-based recommendations are designed to help patients and their loved ones make the best choices, based on the most current evidence and the unified guidance of internationally recognized experts.

Referenced Publication:

Turan TN, Zaidat OO, Gronseth GS, Chimowitz MI, Culebras A, Furlan AJ, Goldstein LB, Gonzalez NR, Latorre JG, Messé SR, Nguyen TN, Sangha RS, Schneck MJ, Singhal AB, Wechsler LR, Rabinstein AA, O’Brien MD, Silsbee H, Fletcher JJ. Stroke Prevention in Symptomatic Large Artery Intracranial Atherosclerosis Practice Advisory. Neurology. 2022;98:486–498. (American Academy of Neurology, AAN). DOI: 10.1212/WNL.0000000000200030