ROME—Carotid stenting was associated with a roughly 30% higher risk of cardiovascular events, compared with carotid endarterectomy, during 12 years of follow-up in a large, real-world, population-based cohort study, Mohamad A. Hussain, MD, reported at the Annual Congress of the European Society of Cardiology. “Our data raise concerns about the external validity of randomized controlled trials of carotid endarterectomy versus stenting and question the potential interchangeability of carotid endarterectomy and stenting as stated in clinical practice guidelines,” said Dr. Hussain, a vascular surgeon at the University of Toronto.
Major practice guidelines cite randomized trial evidence in suggesting that carotid endarterectomy and stenting can be used interchangeably in treating low- or average-risk patients with significant carotid artery disease. Dr. Hussain and his coinvestigators, suspecting that the generalizability of the randomized trial findings might be limited because of operator and institutional selection bias, decided to conduct a retrospective cohort study of all patients older than 40 who underwent carotid endarterectomy or carotid stenting in the province of Ontario from April 2002 through March 2013.
Using validated chart abstraction software, they identified 12,529 patients who had carotid endarterectomy and 1,935 who had carotid stenting. The two groups were similar in terms of most baseline characteristics. Notably, however, stent recipients were significantly more likely to have symptomatic carotid disease and also had more comorbid conditions, as reflected in a higher Charlson Comorbidity Index score.
The primary outcome in the study was the 12-year rate of a composite comprising ischemic stroke, transient ischemic attack (TIA), myocardial infarction, or death. The rate was 35.4% in the carotid endarterectomy group and 44.5% in the stent group. After adjustment for the baseline differences, the stent group still had a statistically significant 28% greater risk of the primary outcome.
“We found the difference remained significant in all of our subgroup analyses, regardless of age, sex, year of procedure, symptomatic or asymptomatic carotid artery disease, CAD [coronary artery disease] or no CAD, diabetes (type 1 or 2) or no diabetes. Outcomes with endarterectomy were always significantly better,” said Dr. Hussain.
“I think our study shows that in clinical practice, we’re not quite seeing the outcomes reported in the clinical trials,” he added.
A Closer Look at the Data
As for the individual components of the composite end point, the 12-year rate of ischemic stroke or TIA was 9% in the carotid endarterectomy group and 14% with stenting, for an adjusted 40% increased risk in the stent group. The 12-year all-cause mortality rate was 26% in the carotid endarterectomy group and 34% with stenting, for an adjusted 28% increased risk. The incidence of myocardial infarction was 8% in both groups.
The investigators next conducted a confirmatory propensity-matched analysis in which 1,927 of the stented patients were closely matched to 3,844 surgical patients, eliminating baseline differences in the prevalence of symptomatic carotid artery disease and other disparities. In this matched cohort, the primary outcome occurred in 37.4% of the carotid endarterectomy group and 44.3% of stent patients, for an adjusted 32% increase in risk in the stented group.
The differences in outcome were driven by sharply higher periprocedural risk in the stented group. After the periprocedural period, the outcome curves remained parallel in the two treatment groups.
In the first 30 days post procedure, the primary composite outcome occurred in 5.4% of the carotid endarterectomy group and 10% of stented patients, for an adjusted 40% increase in relative risk in percutaneously treated patients. The 30-day rate of ischemic stroke or TIA was 3.4% in the surgical group, compared with 6.4% in stented patients. Thirty-day mortality was 0.9% with carotid endarterectomy versus 3.3% with stenting.
Possible Explanations for the Disparity
Asked for his thoughts on the disparity between the results of his real-world study and the major randomized trials of carotid endarterectomy versus stenting, Dr. Hussain replied, “It may be because the trials had high-volume operators at high-volume centers who are experts in carotid stenting, while in the real world, many physicians may not be selecting the right people for carotid stenting.”
Differences in sample size may also figure in the disparity, he continued. He noted that in the recent 10-year report from the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite end point of stroke, myocardial infarction, or death occurred in 9.9% of the carotid endarterectomy group, compared with 11.8% of the stenting group, but this difference in favor of carotid endarterectomy did not achieve statistical significance because of the wide confidence intervals resulting from a smaller sample size than in the Ontario study.
Looking to the future, Dr. Hussain said he thinks the ongoing CREST-2 trial is “important.” It is randomizing patients with asymptomatic high-grade carotid stenosis to uniform intensive medical management either alone or in combination with carotid endarterectomy or stenting with embolic protection. “That study might end up showing us that medical therapy is as good as or even better than stenting or carotid endarterectomy, especially in asymptomatic patients,” he said.
Dr. Hussain reported having no financial conflicts regarding his academically funded study.