ROME – Carotid stenting was associated with a roughly 30% higher risk of cardiovascular events than that of 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 of the University of Toronto.
Bruce Jancin/Frontline Medical News
Dr. Mohamad A. Hussain
Major practice guidelines cite randomized trial evidence in suggesting that CEA and stenting can be used interchangeably in treating low- or average-risk patients with significant carotid artery disease. Dr. Hussain and his coinvestigators, suspicious that the generalizability of the randomized trial findings may be limited because of operator and institutional selection bias, decided to conduct a retrospective cohort study of all patients over age 40 years who underwent CEA 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 CEA and 1,935 with 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), MI, or death. The rate was 35.4% in the CEA 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.
As for the individual components of the composite endpoint, the 12-year rate of ischemic stroke or TIA was 9% in the CEA 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 CEA group and 34% with stenting, for an adjusted 28% increased risk. The incidence of MI 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 CEA 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 that first 30 days post procedure, the primary composite outcome occurred in 5.4% of the CEA 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 CEA versus 3.3% with stenting.
Asked by the award panel for his thoughts on the disparity between the results of his real-world study and the major randomized trials of CEA versus stenting, Dr. Hussain replied, “It may be because the trials had high-volume operators at high-volume centers who are really 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 endpoint of stroke, MI, or death occurred in 9.9% of the CEA group compared with 11.8% of the stenting group (N Engl J Med. 2016 Mar 17;374[11]:1021-31), but this difference in favor of CEA didn’t 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 “very important.” It is randomizing patients with asymptomatic high-grade carotid stenosis to uniform intensive medical management either alone or in combination with CEA 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 CEA, especially in asymptomatic patients,” he said.
Dr. Hussain reported having no financial conflicts regarding his academically funded study.