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

Abstract

This comparative effectiveness study describes the analytical strategy, methods, and results of a target trial emulation examining cohorts of US veterans with carotid stenosis.

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.

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.