ESOC 2023 | Interim data from ECST-2 trial challenges surgical guidelines for carotid stenosis

It’s the second European Carotid Surgery Trial and it started quite a while ago, more than ten years, together with a lot of international investigators. Martin Brown as a PI at the start and now Leo Bonatti, Martin Brown and myself are the PIs. And the question we were going to address is the following. Carotid surgery is done in patients with carotid stenosis based on very solid data. But the trials the current guidelines are based on are old, they’re solid, but they’re old. They are from 20 or 30 years ago. ECST, NASCET, and asymptomatic patient trials. And the decision in the current guidelines to treat a patient, for example, with carotid surgery to prevent them from future strokes is mainly based on the degree of carotid stenosis due to the results of those old trials, and some patient characteristics. In the meantime, medical treatment has improved dramatically. It has improved largely. So our hypothesis was that not all of the patients perhaps should be treated with surgery anymore and that medical treatment could be as good, at least in patients with a low to intermediate risk of future stroke. We thought the high-risk patients should be operated on according to the current guidelines, but the patients with a low or moderate risk may have just enough benefit from optimized medical treatment to date.

So we started ten years ago and initially we planned on a large trial to include maybe even up to 2000 patients and use clinical endpoints. During the course of the trial, it was difficult to enrol so many patients regardless of the enormous effort of all investigators. And during the trial, new developments also came, for example, MRI plaque imaging. It was shown that a vulnerable plaque is a large predictor for recurrent stroke. And by the start of the trial, an interim analysis for a number of higher than 300 patients was planned initially and the steering committee decided after a little bit slow recruitment that we should do this to see the effect now. And also because they thought we thought that new studies should be designed, perhaps including MRI plaque imaging. So we thought the interim analysis was very timely now. So the steering committee even decided to stop enrolment, say, well, do this interim analysis and maybe a final analysis and long term results. And then this will help design new trials.

And so the interim results from the in total 429 patients, they will be presented at ESOC tomorrow. Our hypothesis was that optimized medical treatment alone would be non-inferior to optimized medical therapy plus revascularization because both treatment arms receive optimized medical treatment. It’s just a matter of adding the surgery for the carotid stenosis or not. And according to our hypothesis, the two groups did completely the same at two years. So the event rate at two years was exactly the same. So this is in line with our hypothesis. Also, we did see slightly more harm in the start. So in the first couple of months or half year in the surgery group and then the OMT group later catches up in event rate and they end up with a similar event rate from a composite endpoint which is procedural death, any stroke or myocardial infarction. And they both had an estimated rate of around 10% at two years exactly the same. So yeah, we are very pleased with the results.

I mean, it’s going to help us a lot. So it does show that in this domain of patients there there’s no evidence that you should add surgery to optimized medical treatment to date. We do think we need longer follow up. We also in the paper that will follow soon, hopefully we’ll add silent infarcts on MRI. They are not assessed yet. These are just the clinical endpoints. So those two things are important add-ins, but I don’t think it will change the results. The clinical implication will be that you do not have to offer surgery to all of the patients in this domain. Again, low to intermediate risk, and we think we should design a new prediction rule and the prediction rule will include patient characteristics but also MRI plaque imaging. This has shown to be a very strong predictor for recurrent stroke and we do have plaque imaging done in 240 of the patients in ECST2. It will be a substudy that we will soon analyze as well, so we will know a lot more about that in addition to the diagnostic studies that are known and that is a strong predictor. We think it will end up with a new prediction role more individualized to patients, patient characteristics, symptoms and more plaque characteristics than stenosis degree to reveal the high risk patients that maybe still do need surgery. So the decision to perform surgery will be more will be a more individualized one, I guess than it is now.