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Randomized Controlled Trial
. 2020 Sep 1;77(9):1110-1121.
doi: 10.1001/jamaneurol.2020.1427.

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

Salomeh Keyhani  1   2 , Eric M Cheng  3   4 , Katherine J Hoggatt  1   2 , Peter C Austin  5 , Erin Madden  6 , Paul L Hebert  7   8 , Ethan A Halm  9   10   11 , Ayman Naseri  2   12 , Jason M Johanning  13   14 , Danielle Mowery  15   16   17 , Wendy W Chapman  18 , Dawn M Bravata  19   20   21
Affiliations
Randomized Controlled Trial

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

Salomeh Keyhani et al. JAMA Neurol. .

Erratum in

  • Mislabeled Curves in a Figure.
    [No authors listed] [No authors listed] JAMA Neurol. 2020 Sep 1;77(9):1179. doi: 10.1001/jamaneurol.2020.2784. JAMA Neurol. 2020. PMID: 32716478 Free PMC article. No abstract available.

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Cheng reported receiving grants from the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) during the conduct of the study. Dr Johanning reported holding a licensed patent to FUTUREASSURE LLC. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Carotid Cohort Construction
CAS indicates carotid artery stenting; CEA, carotid endarterectomy; RCT, randomized clinical trial; and TIA, transient ischemic attack.
Figure 2.
Figure 2.. Survival Probability for Fatal and Nonfatal Strokes in the Pragmatic Sample
Figure 3.
Figure 3.. Cumulative Incidence Function of Fatal and Nonfatal Stroke in the Pragmatic Sample
See this image and copyright information in PMC

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References

    1. Hobson RW II, Weiss DG, Fields WS, et al. ; Veterans Affairs Cooperative Study Group . Efficacy of carotid endarterectomy for asymptomatic carotid stenosis. N Engl J Med. 1993;328(4):221-227. doi:10.1056/NEJM199301283280401 - DOI - PubMed
    1. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study Endarterectomy for asymptomatic carotid artery stenosis. JAMA. 1995;273(18):1421-1428. doi:10.1001/jama.1995.03520420037035 - DOI - PubMed
    1. Halliday A, Mansfield A, Marro J, et al. ; MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group . Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet. 2004;363(9420):1491-1502. doi:10.1016/S0140-6736(04)16146-1 - DOI - PubMed
    1. Barnett HJM, Taylor DW, Haynes RB, et al. ; North American Symptomatic Carotid Endarterectomy Trial Collaborators . Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med. 1991;325(7):445-453. doi:10.1056/NEJM199108153250701 - DOI - PubMed
    1. European Carotid Surgery Trialists’ Collaborative Group MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. Lancet. 1991;337(8752):1235-1243. doi:10.1016/0140-6736(91)92916-P - DOI - PubMed

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