Extolling the benefits of evidence-based practice, timely surgical intervention and intensive medical therapy, Dominic PJ Howard (Oxford, UK) spoke at the Vascular Society of Great Britain and Ireland’s (VSGBI) 2023 annual scientific meeting (VSASM; 22–24 November, Dublin, Ireland) on what needs to be known regarding carotid disease management.
The consultant vascular surgeon at Oxford University Hospitals NHS Foundation Trust first addressed whether clinicians should be operating on any patients with carotid disease. “We know from the NASCET, ECST and Veterans Affairs trials that early intervention for patients with high-grade symptomatic stenosis is very effective at preventing strokes,” Howard said. The presenter did point out, however, that these trials are over 30 years old.
Howard stressed that advances in medical therapy over the last two decades have been “significant,” highlighting that some studies have suggested intensive medical therapy can reduce stroke risk by up to 80% in patients presenting with minor events.
The presenter also highlighted interim results from ECST-2, presented earlier last year, which found that at two years there was no obvious benefit of revascularisation on top of medical therapy for carotid patients. However, he urged audience members to be aware that ECST-2 did struggle with funding, recruiting only 400 out of a planned 2,000 patients, and only randomised low-risk patients—both symptomatic and asymptomatic—with moderate stenosis.
Sharing some data supporting the notion that medical therapy alone may be adequate to treat symptomatic carotid patients, Howard pointed to a pooled analysis of older versus newer randomised trials looking at intervention. The data showed that, for patients on medical therapy whilst awaiting intervention, there is a “reasonably high” stroke risk over 120 days; in the newer trials, on the other hand, the stroke risk on medical therapy whilst awaiting intervention “appears to be very low, at around 2%”. Howard did urge caution with interpreting these data, however. “These events were only those that were collected after randomisation, and the majority of patients in these trials were randomised beyond two weeks of index event,” he shared with VSASM 2023.
Howard then referenced an ad hoc analysis of the POINT trial, which looked at dual antiplatelets versus aspirin for prevention of recurrent stroke. “We can see that dual antiplatelet therapy does reduce the risk of recurrent events in patients without carotid disease, and also in patients with symptomatic disease,” he informed the audience. The presenter did identify an “elephant in the room” in this analysis, however, which is the fact that patients with symptomatic carotid disease, despite dual antiplatelet therapy, have a much higher recurrent stroke risk than those without carotid disease.
“We also have to be aware that our surgical risks have come down,” Howard stressed. Over the last two decades, he specified that procedural risks have more than halved with regard to stroke or death in the perioperative period. “We might say it’s simply because we got better at operating; I think it’s probably because of better medical therapy before and after operating, and also possibly due to higher volume centres performing more operations,” the presenter opined.
Patient compliance
The lack of patient compliance with various therapies was also addressed. Howard detailed: “Intensive medical therapy, intensive exercise and a Mediterranean diet are fantastic for our patients, but patient compliance with intensive medical therapy is less than 50%, one-third of our patients are found to have antiplatelet resistance in studies—and yet we don’t test for this so we don’t know whether we’re giving them optimal medical therapy or not—and compliance with lifestyle and exercise, which are arguably the most important interventions, is less than 10%.”
At this point, Howard acknowledged that trial participants may not necessarily represent the typical patient seen in the clinic. Here, the presenter referenced the 20-year OxVasc study. In 100,000 patients, Howard relayed that he and colleagues identified a “dramatic” fall in the rate of recurrent events. The presenter suggested that while this will be due partly to improvements in medical therapy, the results will also stem from the fact that patients are receiving treatment sooner.
“This brings us on to the fact that we are too slow,” Howard stated. “In fact, we’re getting slower.” In light of this, Howard urged: “If we’re going to treat people and give them maximum benefit from urgent intervention, we have to prioritise carotid surgery for symptomatic patients as an emergency procedure and put them on the next operating list.”
Here, Howard called attention to a “very exciting” trial in the pipeline—COMET—which will be running from Leicester, UK, and will look at randomising patients with symptomatic stenosis to endarterectomy versus best medical therapy.
Timing of intervention
Howard then turned his focus to timing of intervention after symptom onset. He reported that, when this topic was first looked at, it was Swedish registry data that suggested operating within the first few days of an event was “very risky”. In the data, he specified, stroke or death was over 10% for those operated on within 48 hours. Despite this, the presenter relayed that larger datasets from the UK and Germany have now quelled concerns. “Actually, the event rates appear to be pretty similar to those patients operated on beyond 48 hours,” he communicated.
Conversely, Howard stated that early stenting, i.e. stenting within seven days of an event, “appears to be quite dangerous”. Referencing a pooled analysis of interventional trials, the presenter shared that patients receiving a stent within seven days have an 8.4% risk of stroke or death compared to 1.3% for those undergoing urgent endarterectomy.
The presenter then moved on to a “more common problem” faced by clinicians in day-to-day practice: the question of whether to operate following thrombolysis or mechanical thrombectomy. He mentioned that Ross Naylor (Leicester, UK) and colleagues conducted a meta-regression analysis on the topic, concluding that the safest time to operate on these patients appears to be at around six days post thrombolysis.
Looking at what the guidelines say, Howard shared that the new European recommendations continue with their advice that symptomatic patients who have greater than 50% stenosis should be considered for intervention (endarterectomy, not stenting) as soon as possible. There is a new recommendation in these guidelines, however, which says that a clinician should consider operating on patients receiving thrombolysis, but should wait six days before initiating surgery.
Finally, Howard looked at whether there is any way of selecting asymptomatic patients for intervention. He mentioned the ACST trial, which did show that patients on triple therapy—antithrombotics, blood pressure control and statins—benefitted from intervention over a five- and 10-year period.
The European guidelines, the presenter noted, suggest using a variety of criteria to try and help select patients who may benefit from intervention. “The problem is that most of us don’t have these investigations available to us in our normal practice,” he remarked.
In order to try and get a definitive answer to this question, Howard pointed to a study he and colleagues recently had published in The Lancet, which looked at whether degree of stenosis may be predictive and help with decision making. “We found that, over the last 20 years, patients with high-grade asymptomatic stenosis have always had a two-to-three-fold increased risk of stroke compared to those with moderate stenosis,” he reported. “And this would appear to be a linear increase—as the degree of stenosis increases, so does the ipsilateral stroke risk.”
In view of this study, the presenter noted that the American guidelines have changed their recommendation to now suggest that asymptomatic patients with greater than 70% stenosis should be considered for intervention if they have a low surgical risk and a good life expectancy.
Summarising, Howard put forward that intervention for symptomatic carotid disease is “under scrutiny” in view of improvements in medical therapy. However, one of his key messages was thus: “If we’re going to operate on these patients, we should still be evidence based.” The presenter continued that, at the moment, operating as soon as possible is important, yet time from event to intervention is currently too slow. “Urgent endarterectomy is safe but urgent stenting is not,” was another key message, and Howard closed with the statement that “all patients require intensive medical therapy and lifestyle changes”.
