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CME / ABIM MOC / CE

Is Vulnerable Carotid Plaque Linked to Recurrent Stroke?

  • Authors: News Author: Sue Hughes; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 7/8/2022
  • THIS ACTIVITY HAS EXPIRED FOR CREDIT
  • Valid for credit through: 7/8/2023, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for cardiologists, critical care clinicians, neurologists, family medicine and primary care clinicians, nurses, nurse practitioners, internists, physician assistants, and other members of the health care team who treat and manage patients with stroke.

The goal of this activity is for learners to be better able to describe the association of complicated carotid artery plaque ipsilateral to acute ischemic anterior circulation stroke with recurrent ischemic stroke or transient ischemic attack, based on the CAPIAS (Carotid Plaque Imaging in Acute Stroke) multicenter study by Kopczak and colleagues.

Upon completion of this activity, participants will:

  • Assess the association of ipsilateral complicated carotid artery plaque with recurrent ischemic stroke or transient ischemic attack, based on the Carotid Plaque Imaging in Acute Stroke prospective, multicenter study
  • Evaluate the clinical implications of the association of ipsilateral complicated carotid artery plaque with recurrent ischemic stroke or transient ischemic attack, based on the Carotid Plaque Imaging in Acute Stroke prospective, multicenter study
  • Outline implications for the healthcare team


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News Author

  • Sue Hughes

    Journalist
    Medscape Medical News

    Disclosures

    Sue Hughes has no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Laurie Barclay, MD, has the following relevant financial relationships:
    Formerly owned stocks in: AbbVie

Editor/Compliance Reviewer

  • Yaisanet Oyola, MD

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Yaisanet Oyola, MD, has no relevant financial relationships.

Compliance Reviewer

  • Lisa Simani, APRN, MS, ACNP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Lisa Simani, APRN, MS, ACNP, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.


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CME / ABIM MOC / CE

Is Vulnerable Carotid Plaque Linked to Recurrent Stroke?

Authors: News Author: Sue Hughes; CME Author: Laurie Barclay, MDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED FOR CREDIT

CME / ABIM MOC / CE Released: 7/8/2022

Valid for credit through: 7/8/2023, 11:59 PM EST

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Clinical Context

Stroke is a leading cause of death, disability, and cognitive decline. Recurrence rates vary depending on stroke etiology.

In patients with symptomatic carotid artery stenosis, high-risk features of carotid artery plaque, particularly intraplaque hemorrhage, on magnetic resonance imaging (MRI) have been linked to increased risk for recurrent ischemic stroke or transient ischemic attack (TIA). Because of study limitations, however, risks associated with complicated carotid artery plaques in the acute phase of stroke are still unknown.

Study Synopsis and Perspective

Small but vulnerable carotid plaques appear to be a more important cause of stroke than previously thought, a new study suggests.

Results of the Carotid Plaque Imaging in Acute Stroke (CAPIAS) study show that patients with complicated carotid artery plaques ipsilateral to acute ischemic anterior circulation stroke had an increased risk for recurrent ischemic stroke.

"This study found ipsilateral [complicated carotid artery plaques] as detected by high-resolution MRI within 10 days from ischemic stroke onset to be associated with a higher risk of recurrent ischemic stroke or TIA. The results were driven by the results in cryptogenic stroke patients and by events ipsilateral to the index stroke," the authors report.

"Carotid plaque imaging identifies high-risk patients who might be suited for inclusion into future secondary prevention trials," they conclude.

The study, led by Anna Kopczak, MD, from the University Hospital, LMU Munich, is published in the June 7 issue of the Journal of the American College of Cardiology.[1]

In an accompanying editorial, Joshua Z. Willey, MD, and Gerard Pasterkamp, MD, say the study "highlights the importance of considering substenotic atherosclerotic plaques as a cause of ischemic stroke and the subsequent risk of recurrence, and it broadens our understanding of the concept of [embolic stroke of undetermined source]."[2]

Dr Willey explained that about 30% of patients with stroke have an embolic stroke of undermined source, and although there is quite a good understanding of cardiac sources of embolic stroke, this study suggests that carotid plaques could be contributing more than previously thought to these types of strokes.

Dr Willey also noted that at present, only patients with carotid stenosis greater than 50% are considered for surgery or more aggressive treatment.

"This study has done a very nice job showing that smaller plaques can be a source of stroke; members of the health care team must be aware that patients with these smaller but vulnerable plaques may need to be considered for more tests and secondary preventative treatments," he added.

Recurrent Events

The CAPIAS study prospectively recruited patients in the 10 days after an ischemic stroke restricted to the territory of a single carotid artery who underwent multisequence, contrast-enhanced MRI to identify complicated carotid artery plaques. These were defined by the presence of a ruptured fibrous cap, intraplaque hemorrhage, or mural thrombus.

Among 196 patients enrolled, 104 were found to have had a cryptogenic stroke and had smaller nonstenosing carotid artery plaques.

Recurrent events were significantly more frequent in patients with complicated carotid artery plaques than in those without such plaques, both in the overall cohort (incidence rate, 9.50 vs 3.61 per 100 patient-years) and in patients with cryptogenic stroke (10.92 vs 1.82 per 100 patient-years). The results were driven by ipsilateral events.

Among patients with cryptogenic stroke, those with ipsilateral complicated carotid artery plaques had a 5.6-fold increased risk for recurrent ischemic stroke or TIA compared with those without such plaques, the authors report, with the presence of an ipsilateral ruptured fibrous cap and of intraplaque hemorrhage significantly associated with recurrent ischemic stroke or TIA.

The researchers say that the most important finding in terms of clinical implications in the study is the association between intraplaque hemorrhage and an increased risk for recurrent ischemic stroke or TIA in patients with cryptogenic stroke.

They point out that unlike other features of complicated carotid artery plaques, intraplaque hemorrhage can be reliably detected by standard coils and conventional native T1-weighted sequences, indicating that MRI for intraplaque hemorrhage detection could be integrated into the diagnostic workflow of anterior circulation stroke.

They suggest that the next step should be a multicenter study to determine the precise prevalence of intraplaque hemorrhage and associated recurrence rates in unselected patients with anterior circulation stroke.

"At present, there is a perception that if the carotid plaque is causing less than a 50% stenosis, then this is not directly related to the stroke," Dr Willey commented. "But this study shows this not to be the case and that we need to think more carefully about patients with smaller carotid plaques. This study showed that vulnerable carotid plaques are particularly dangerous, and at the moment, these plaques are not being identified and treated.

"This opens up a new group of patients for whom more aggressive secondary preventative therapy may be required. This observation makes sense, as it parallels what we know about coronary disease," he added.

Dr Willey noted that this study raises the issue of whether patients with smaller carotid plaques could benefit from more advanced imaging to identify those with vulnerable plaques, but he pointed out that the study needs to be replicated in a more diverse population of patients to better understand the degree to which this affects different groups.

He explained that the proportion of embolic strokes of unknown source that will originate from vulnerable carotid plaques is hard to define and will vary between different populations.

"Older patients are more likely to have a stroke caused by undiagnosed [atrial fibrillation]. But patients with a high burden of risk factors, such as smoking, diabetes, or high cholesterol, are more likely to have vulnerable plaque. I suspect rates of vulnerable carotid plaques among [embolic stroke of undetermined source] patients could be around 30% or more in these types of patients," Dr Willey said.

Study Highlights

  • CAPIAS prospectively recruited patients with ischemic stroke restricted to a single carotid artery territory.
  • Multisequence, contrast-enhanced carotid MRI within 10 days from stroke onset defined complicated carotid artery plaques.
  • Recurrent ischemic stroke or TIA was the primary outcome.
  • Of 196 patients enrolled, 104 had cryptogenic stroke and nonstenosing carotid artery plaque.
  • During follow-up (mean, 30 months), 21 patients had recurrent ischemic stroke or TIA.
  • Ipsilateral intraplaque hemorrhage occurred in 27% of patients with cryptogenic stroke and 26% of the overall sample.
  • Recurrent events were significantly more frequent in patients with vs without ipsilateral complicated carotid artery plaque in the overall cohort (incidence [3-year interval]: 9.50 vs 3.61/100 patient-years; P=.025) and in patients with cryptogenic stroke (10.92 vs 1.82/100 patient-years; P=.003).
  • This finding was driven by ipsilateral events.
  • In patients with cryptogenic stroke, ruptured fibrous cap (HR, 4.91; 95% confidence interval [CI], 1.31-18.45; P=.018) and intraplaque hemorrhage (HR, 4.37; 95% CI, 1.20-15.97; P=.026) were associated with significantly increased risk for recurrent events.
  • Among patients with cryptogenic stroke, those with vs without ipsilateral complicated carotid artery plaque had 5.6-fold increased risk for recurrent ischemic stroke or TIA.
  • Among patients with recurrent ischemic stroke or TIA, 52.4% had been classified as having cryptogenic stroke.
  • In Cox regression models adjusting for age and sex, ipsilateral complicated carotid artery plaque was associated with 2.5-fold increased risk for recurrent ischemic stroke or TIA over the course of 3 years (HR, 2.51; 95% CI, 1.03-6.11; P=.043); for ipsilateral recurrent ischemic stroke or TIA, HR was 3.37 (95% CI, 1.21-9.38; P=.020).
  • The investigators concluded that ipsilateral complicated carotid artery plaque is associated with increased risk for recurrent ischemic stroke or TIA.
  • Carotid artery plaque imaging identifies high-risk patients who may be suitable for future secondary prevention trials.
  • Standard coils and conventional native T1-weighted sequences can detect intraplaque hemorrhage, but not other characteristics of complicated carotid artery plaque, suggesting that MRI imaging for intraplaque hemorrhage could easily be included in the diagnostic workup of anterior circulation stroke.
  • The relatively high prevalence of ipsilateral intraplaque hemorrhage suggests that this marker is potentially useful for risk stratification and patient selection for clinical trials.
  • Embolic stroke of undetermined source may be an underlying cause of approximately 30% of strokes.
  • This study suggests that carotid plaques may be more of an underlying cause of embolic stroke of undetermined source than previously thought.
  • Although stroke in older patients more often results from undiagnosed atrial fibrillation, vulnerable plaque more often causes embolic stroke of undetermined source in patients with multiple risk factors, including smoking, diabetes or high cholesterol.
  • Although only patients with more than 50% carotid stenosis are now considered for surgery or more aggressive treatment, this study suggests that patients with smaller but vulnerable plaques may need to be considered for more tests and secondary preventive treatments, especially as treatment options for cryptogenic stroke are limited.
  • Study limitations include participants selected for carotid artery plaque who had relatively mild strokes, mandating additional studies, such as, first, a multicenter study examining intraplaque hemorrhage prevalence and associated recurrence in unselected patients with anterior circulation stroke.
  • Other limitations include long recruitment, relatively few female patients, limited age range, and exclusion of patients with carotid artery plaque smaller than 2 mm, limiting the results to patients with stroke with some degree of atherosclerosis.

Clinical Implications

  • Ipsilateral complicated carotid artery plaque is associated with increased risk for recurrent ischemic stroke or TIA.
  • Carotid plaque imaging identifies high-risk patients who may be suitable for future secondary prevention trials.
  • Implications for the Health Care Team: Patients with smaller but vulnerable plaques may need more tests and secondary preventive treatments, especially as treatment options for cryptogenic stroke are limited.

 

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