Comparative Effectiveness of Carotid Endarterectomy vs Initial Medical Therapy in Patients With Asymptomatic Carotid Stenosis | Cerebrovascular Disease | JAMA Neurology | JAMA Network
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    Original Investigation
    June 1, 2020

    Comparative Effectiveness of Carotid Endarterectomy vs Initial Medical Therapy in Patients With Asymptomatic Carotid Stenosis

    Author Affiliations
    • 1Division of General Internal Medicine, Department of Medicine, University of California San Francisco, San Francisco
    • 2San Francisco Veterans Affairs (VA) Medical Center, San Francisco, California
    • 3Department of Neurology, UCLA (University of California Los Angeles), Los Angeles
    • 4VA Greater Los Angeles Healthcare System, Los Angeles, California
    • 5Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
    • 6Northern California Institute of Research and Education, San Francisco
    • 7University of Washington, Seattle
    • 8Puget Sound VA, Seattle, Washington
    • 9Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas
    • 10Department of Population, University of Texas Southwestern Medical Center, Dallas
    • 11Department of Data Science, University of Texas Southwestern Medical Center, Dallas
    • 12Department of Ophthalmology, University of California San Francisco, San Francisco
    • 13Department of Surgery, University of Nebraska, Omaha
    • 14Omaha VA Medical Center, Omaha, Nebraska
    • 15Biomedical Informatics, University of Utah, Salt Lake City
    • 16Salt Lake City VA Health Care System, Salt Lake City, Utah
    • 17Now with Department of Biostatistics, Epidemiology, & Informatics, University of Pennsylvania, Philadelphia
    • 18University of Melbourne, Melbourne, Victoria, Australia
    • 19Department of Medicine, Indiana University School of Medicine, Indianapolis
    • 20Department of Neurology, Indiana University School of Medicine, Indianapolis
    • 21Richard L. Roudebush VA Medical Center, Indianapolis, Indiana
    JAMA Neurol. 2020;77(9):1110-1121. doi:10.1001/jamaneurol.2020.1427
    Key Points

    Question  Among patients with asymptomatic carotid stenosis, is carotid endarterectomy superior to initial medical therapy in preventing fatal and nonfatal stroke within 5 years of follow-up in real-world practice?

    Findings  In this comparative effectiveness study of 5221 patients with asymptomatic carotid stenosis, the absolute reduction in the risk of fatal and nonfatal strokes associated with early carotid endarterectomy treatment was less than half the reduction observed in trials initiated more than 2 decades ago. The decrease was not statistically significant when the competing risk of nonstroke deaths was accounted for in the analysis.

    Meaning  Results of this study suggest that, given the up-front perioperative risks associated with carotid endarterectomy and the reduced benefit derived from revascularization, initial medical therapy may be an acceptable treatment strategy for the management of asymptomatic carotid stenosis.


    Importance  Carotid endarterectomy (CEA) among asymptomatic patients involves a trade-off between a higher short-term perioperative risk in exchange for a lower long-term risk of stroke. The clinical benefit observed in randomized clinical trials (RCTs) may not extend to real-world practice.

    Objective  To examine whether early intervention (CEA) was superior to initial medical therapy in real-world practice in preventing fatal and nonfatal strokes among patients with asymptomatic carotid stenosis.

    Design, Setting, and Participants  This comparative effectiveness study was conducted from August 28, 2018, to March 2, 2020, using the Corporate Data Warehouse, Suicide Data Repository, and other databases of the US Department of Veterans Affairs. Data analyzed were those of veterans of the US Armed Forces aged 65 years or older who received carotid imaging between January 1, 2005, and December 31, 2009. Patients without a carotid imaging report, those with carotid stenosis of less than 50% or hemodynamically insignificant stenosis, and those with a history of stroke or transient ischemic attack in the 6 months before index imaging were excluded. A cohort of patients who received initial medical therapy and a cohort of similar patients who received CEA were constructed and followed up for 5 years. The target trial method was used to compute weighted Kaplan-Meier curves and estimate the risk of fatal and nonfatal strokes in each cohort in the pragmatic sample across 5 years of follow-up. This analysis was repeated after restricting the sample to patients who met RCT inclusion criteria. Cumulative incidence functions for fatal and nonfatal strokes were estimated, accounting for nonstroke deaths as competing risks in both the pragmatic and RCT-like samples.

    Exposures  Receipt of CEA vs initial medical therapy.

    Main Outcomes and Measures  Fatal and nonfatal strokes.

    Results  Of the total 5221 patients, 2712 (51.9%; mean [SD] age, 73.6 [6.0] years; 2678 men [98.8%]) received CEA and 2509 (48.1%; mean [SD] age, 73.6 [6.0] years; 2479 men [98.8%]) received initial medical therapy within 1 year after the index carotid imaging. The observed rate of stroke or death (perioperative complications) within 30 days in the CEA cohort was 2.5% (95% CI, 2.0%-3.1%). The 5-year risk of fatal and nonfatal strokes was lower among patients randomized to CEA compared with patients randomized to initial medical therapy (5.6% vs 7.8%; risk difference, −2.3%; 95% CI, −4.0% to −0.3%). In an analysis that incorporated the competing risk of death, the risk difference between the 2 cohorts was lower and not statistically significant (risk difference, −0.8%; 95% CI, −2.1% to 0.5%). Among patients who met RCT inclusion criteria, the 5-year risk of fatal and nonfatal strokes was 5.5% (95% CI, 4.5%-6.5%) among patients randomized to CEA and was 7.6% (95% CI, 5.7%-9.5%) among those randomized to initial medical therapy (risk difference, −2.1%; 95% CI, −4.4% to −0.2%). Accounting for competing risks resulted in a risk difference of −0.9% (95% CI, −2.9% to 0.7%) that was not statistically significant.

    Conclusions and Relevance  This study found that the absolute reduction in the risk of fatal and nonfatal strokes associated with early CEA was less than half the risk difference in trials from 20 years ago and was no longer statistically significant when the competing risk of nonstroke deaths was accounted for in the analysis. Given the nonnegligible perioperative 30-day risks and the improvements in stroke prevention, medical therapy may be an acceptable therapeutic strategy.