MUNICH – , suggests a planned interim analysis of ECST-2.
Almost 430 patients with symptomatic and asymptomatic atherosclerotic carotid stenosis greater than or equal to 50% and a Carotid Artery Risk (CAR) score less than 20% were randomly assigned to OMT alone or OMT plus revascularization with carotid endarterectomy (CEA) or carotid artery stenting.
The study, which was presented at the annual European Stroke Organisation Conference, was stopped early because of slow recruitment.
Nevertheless, the current results showed that there was no significant difference at 2 years between the treatment groups in the rate of a composite endpoint, as well as the occurrence of any stroke, myocardial infarction, and periprocedural death.
In other words, “there was no evidence of benefit at 2 years from additional carotid revascularization” in patients with carotid stenosis who had a low to intermediate predicted stroke risk, said study presenter Paul Nederkoorn, MD, PhD, department of neurology, Amsterdam UMC, University of Amsterdam.
He added, however, that the complete 2 years will include additional analyses, including an analysis of silent infarcts on MRI, which may affect the results, and that longer clinical follow-up is required.
Future work will include the design and validation of a novel stroke risk prediction tool that will include MRI plaque imaging and will allow individualized patient selection for revascularization, as well as a cost-effectiveness analysis, he noted.
Conclusions ‘difficult’
Session co-chair Peter Kelly, MD, professor of neurology at Mater University Hospital/University College Dublin, and president-elect of the European Stroke Association, described the findings as “interesting” and that it was “great to see them.”
“I’m sure we’ll be discussing these results for a while,” he added.
But co-chair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the Stroke Unit, department of neurology, Oslo University Hospital, said that it’s “difficult to draw firm conclusions from the trial.”
The patients were highly selected, recruitment was “perhaps a bit too slow,” and the study was probably conducted over too many sites, she said in an interview.
Dr. Sandset also noted that the options available for OMT have changed over the course of the study, as well as the overall approach to management.
“We are more aware of how we should treat” these patients, and “we’re probably a bit more aggressive,” which will have shifted the outcomes in the comparator arm as the study progressed.
“That is the challenge of doing these trials that take many years to run – our practice changes.”
‘Old evidence’
In his presentation, Dr. Nederkoorn pointed out that, while the current guidelines for CEA are “robust,” they are based on “old evidence” from trials conducted 20-30 years ago.
During that time, he said, medical treatment has improved significantly, and the risk for stroke has approximately halved. Yet the decision to perform CEA is still largely based on the degree of stenosis and the patient’s symptom status.
Dr. Nederkoorn suggested, however, that factors such as plaque ulceration and patient characteristics and comorbidities might influence the risk-benefit ratio for revascularization.
The current trial was therefore established to test the hypothesis that patients with carotid stenosis greater than or equal to 50% and a low to intermediate risk of stroke will not benefit from additional carotid revascularization on top of optimized medical therapy.
The team conducted a prospective, multicenter, open clinical trial in which patients with both symptomatic and asymptomatic atherosclerotic carotid stenosis were randomly assigned to revascularization plus OMT or OMT alone.
Dr. Nederkoorn explained that a low to intermediate 5-year risk for stroke was established using the CAR score less than 20%.
This is based on a range of parameters, including the sex and age of the patient, degree of stenosis, the type of and time since the event, and the presence of comorbidities, among other factors.
He said that the data was originally derived from the NASCET trial, which was published in 1998, and the first ECST trial, published in the same year.
Since then, the risk of ipsilateral stroke has “strongly declined,” Dr. Nederkoorn said, and so the CAR score was recalibrated to reflect the likely benefit of current OMT.
For the trial, OMT included antihypertensive and cholesterol-lowering medications, and dietary changes, alongside antiplatelet agents and anticoagulation, if indicated, to achieve predefined, guideline-led lipid and blood pressure targets.
Revascularization included CEA and coronary artery stenting in selected patients and was recommended to be performed within 2 weeks of randomization in symptomatic patients and within 4 weeks in asymptomatic patients.
When the trial started in 2012, the intention was to recruit 2,000 patients, with a planned interim analysis after enrollment of 320 patients.
However, recruitment was suspended in 2019, with 429 patients having been enrolled, as it was clear that achieving a cohort of 2,000 patients was “not practical without a change in the trial design” to include MRI plaque imaging and without further funding.
Dr. Nederkoorn showed that the baseline characteristics of the OMT and revascularization plus OMT groups were comparable. The average age of the patients in the groups was 71-72 years, and 31% were female.
Symptomatic disease was present in about 40% of patients, and about 76% had hypertension. Type 2 diabetes was reported in roughly one-quarter of the patients.
There was no difference in the time from randomization to the revascularization procedure between patients with asymptomatic and symptomatic disease.
Moving to the primary outcome, which was a composite of periprocedural death within 90 days of randomization and clinically manifest stroke or myocardial infarction at 2 years, Dr. Nederkoorn showed that there was no significant difference between the treatment groups.
Despite a suggestion that patients undergoing revascularization experienced “more harm” in the initial follow-up period, particularly in patients with a CAR score greater than 10%, the event curves met at around 18 months.
Overall, the hazard ratio between revascularization plus OMT versus OMT alone was 0.96 (95% confidence interval, 0.53-1.76, P = .90).
Breaking down the composite endpoint, there was a numerically lower rate of any stroke with OMT alone, compared with revascularization plus OMT over the study period, but again the difference was not significant at 2 years, at a hazard ratio of 0.68 (95% CI, 0.32-1.42, P = .30).
There was only one case of periprocedural death, in the revascularization arm. Although myocardial infarction was numerically twice as likely with OMT alone, compared with the combined intervention arm, the difference was not significant, at a hazard ratio of 2.00 (95% CI, 0.68-5.84, P = .21).
The study was funded by the National Institute for Health and Care Research, the Swiss National Science Foundation, The Netherlands Organisation of Scientific Research, and the Leeds Neurology Foundation. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.