Joseph Kamtchum-Tatuene1, Jean Jacques Noubiap2, Alan H Wilman3, Maher Saqqur4, Ashfaq Shuaib4, Glen C Jickling4. 1. Neuroscience and Mental Health Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada. 2. Centre for Heart Rhythm Disorders, South Australian Health and Medical Research Institute, Royal Adelaide Hospital, The University of Adelaide, Adelaide, South Australia, Australia. 3. Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada. 4. Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Abstract
Importance: There is an ongoing debate regarding the management of asymptomatic carotid stenosis. Previous studies have reported imaging features of high-risk plaques that could help to optimize the risk-benefit ratio of revascularization. However, such studies have not provided an accurate estimate of the prevalence of high-risk plaques and the associated annual incidence of ipsilateral ischemic cerebrovascular events to inform the design of clinical trials using a risk-oriented selection of patients before randomization. Objective: To assess the relevance and feasibility of risk-oriented selection of patients for revascularization. Data Sources: A systematic search of PubMed and Ovid Embase from database inception to July 31, 2019, was performed. Study Selection: Prospective observational studies that reported prevalence of high-risk plaques and incidence of ipsilateral ischemic cerebrovascular events were included. Data Extraction and Synthesis: Aggregated data were pooled using random-effects meta-analysis. Data were analyzed from December 16, 2019, to January 15, 2020. Main Outcomes and Measures: Prevalence of high-risk plaques and annual incidence of ipsilateral ischemic events. Results: Overall, 64 studies enrolling 20 751 participants aged 29 to 95 years (mean age range, 55.0-76.5 years; proportion of men, 45%-87%) were included in the meta-analysis. Among all participants, the pooled prevalence of high-risk plaques was 26.5% (95% CI, 22.9%-30.3%). The most prevalent high-risk plaque features were neovascularization (43.4%; 95% CI, 31.4%-55.8%) in 785 participants, echolucency (42.3%; 95% CI, 32.2%-52.8%) in 12 364 participants, and lipid-rich necrotic core (36.3%; 95% CI, 27.7%-45.2%) in 3728 participants. The overall incidence of ipsilateral ischemic cerebrovascular events was 3.2 events per 100 person-years (22 cohorts with 10 381 participants; mean follow-up period, 2.8 years; range, 0.7-6.5 years). The incidence of ipsilateral ischemic cerebrovascular events was higher in patients with high-risk plaques (4.3 events per 100 person-years; 95% CI, 2.5-6.5 events per 100 person-years) than in those without high-risk plaques (1.2 events per 100 person-years; 95% CI, 0.6-1.8 events per 100 person-years), with an odds ratio of 3.0 (95% CI, 2.1-4.3; I2 = 48.8%). In studies focusing on severe stenosis (9 cohorts with 2128 participants; mean follow-up period, 2.8 years; range, 1.4-6.5 years), the incidence of ipsilateral ischemic cerebrovascular events was 3.7 events per 100 person-years (95% CI, 1.9-6.0 events per 100 person-years). The incidence of ipsilateral ischemic cerebrovascular events was also higher in patients with high-risk plaques (7.3 events per 100 person-years; 95% CI, 2.0-15.0 events per 100 person-years) than in those without high-risk plaques (1.7 events per 100 person-years; 95% CI, 0.6-3.3 events per 100 person-years), with an odds ratio of 3.2 (95% CI, 1.7-5.9; I2 = 39.6%). Conclusions and Relevance: High-risk plaques are common in patients with asymptomatic carotid stenosis, and the associated risk of an ipsilateral ischemic cerebrovascular event is higher than the currently accepted estimates. Extension of routine assessment of asymptomatic carotid stenosis beyond the grade of stenosis may help improve risk stratification and optimize therapy.
Importance: There is an ongoing debate regarding the management of asymptomatic carotid stenosis. Previous studies have reported imaging features of high-risk plaques that could help to optimize the risk-benefit ratio of revascularization. However, such studies have not provided an accurate estimate of the prevalence of high-risk plaques and the associated annual incidence of ipsilateral ischemic cerebrovascular events to inform the design of clinical trials using a risk-oriented selection of patients before randomization. Objective: To assess the relevance and feasibility of risk-oriented selection of patients for revascularization. Data Sources: A systematic search of PubMed and Ovid Embase from database inception to July 31, 2019, was performed. Study Selection: Prospective observational studies that reported prevalence of high-risk plaques and incidence of ipsilateral ischemic cerebrovascular events were included. Data Extraction and Synthesis: Aggregated data were pooled using random-effects meta-analysis. Data were analyzed from December 16, 2019, to January 15, 2020. Main Outcomes and Measures: Prevalence of high-risk plaques and annual incidence of ipsilateral ischemic events. Results: Overall, 64 studies enrolling 20 751 participants aged 29 to 95 years (mean age range, 55.0-76.5 years; proportion of men, 45%-87%) were included in the meta-analysis. Among all participants, the pooled prevalence of high-risk plaques was 26.5% (95% CI, 22.9%-30.3%). The most prevalent high-risk plaque features were neovascularization (43.4%; 95% CI, 31.4%-55.8%) in 785 participants, echolucency (42.3%; 95% CI, 32.2%-52.8%) in 12 364 participants, and lipid-rich necrotic core (36.3%; 95% CI, 27.7%-45.2%) in 3728 participants. The overall incidence of ipsilateral ischemic cerebrovascular events was 3.2 events per 100 person-years (22 cohorts with 10 381 participants; mean follow-up period, 2.8 years; range, 0.7-6.5 years). The incidence of ipsilateral ischemic cerebrovascular events was higher in patients with high-risk plaques (4.3 events per 100 person-years; 95% CI, 2.5-6.5 events per 100 person-years) than in those without high-risk plaques (1.2 events per 100 person-years; 95% CI, 0.6-1.8 events per 100 person-years), with an odds ratio of 3.0 (95% CI, 2.1-4.3; I2 = 48.8%). In studies focusing on severe stenosis (9 cohorts with 2128 participants; mean follow-up period, 2.8 years; range, 1.4-6.5 years), the incidence of ipsilateral ischemic cerebrovascular events was 3.7 events per 100 person-years (95% CI, 1.9-6.0 events per 100 person-years). The incidence of ipsilateral ischemic cerebrovascular events was also higher in patients with high-risk plaques (7.3 events per 100 person-years; 95% CI, 2.0-15.0 events per 100 person-years) than in those without high-risk plaques (1.7 events per 100 person-years; 95% CI, 0.6-3.3 events per 100 person-years), with an odds ratio of 3.2 (95% CI, 1.7-5.9; I2 = 39.6%). Conclusions and Relevance: High-risk plaques are common in patients with asymptomatic carotid stenosis, and the associated risk of an ipsilateral ischemic cerebrovascular event is higher than the currently accepted estimates. Extension of routine assessment of asymptomatic carotid stenosis beyond the grade of stenosis may help improve risk stratification and optimize therapy.
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