SONOBIRDIE: Ultrasound Appears to Make Carotid Endarterectomy Safer

Applying ultrasound to help break up thrombus during carotid endarterectomy reduces adverse neurological outcomes in the first 30 days after surgery in patients with either symptomatic or asymptomatic carotid stenosis, according to results from the sham-controlled SONOBIRDIE trial.

In that early period, patients who underwent the procedure accompanied by sonolysis versus a sham intervention saw an absolute 5.5% lower rate of ischemic stroke, TIA, or death (P < 0.001), with no safety concerns, researchers led by David Školoudík, MD, PhD (University of Ostrava, Czechia), reported online recently in the BMJ..

In an imaging substudy, the addition of ultrasound was associated with a lower likelihood of new ischemic lesions identified on brain MRI 24 hours after the operation (8.5% vs 17.4%; P = 0.004).

This is the first randomized controlled trial assessing this approach, and though the results are promising, the impact of sonolysis is not conclusive, Školoudík told TCTMD. “We have to wait for the next trials to write it in guidelines as [a proven] beneficial treatment,” he said.

Indeed, the trial raises some questions, according to Jesse Columbo, MD (Dartmouth Health, Lebanon, NH), who wrote an accompanying editorial. To TCTMD, he pointed to a higher-than-expected rate of adverse outcomes in the control group and to the fact that symptomatic stenosis was not a predictor of outcomes in a multivariable analysis.

“The periprocedural stroke/death risk is so high in the control arm that that makes me worry that it doesn’t totally apply to the patients that I treat in my practice or that we treat in our region,” Columbo said.

“I think that for places that are seeing similar clinical event rates and have similar populations to theirs, perhaps this is a useful intervention,” he added. “But before I would start using it, I would really like to see it performed in a study population that is more representative of the people that I treat, with the stroke/death risks that I’m used to, and still show a benefit.”

The SONOBIRDIE Trial

Although ultrasound has been used widely for diagnostic and surveillance purposes, there is also evidence from in vitro, animal, and some human studies that it can be used to enhance thrombus dissolution, either through a direct mechanical effect, activation of the body’s fibrinolytic system, or other potential mechanisms.

Pilot studies have shown it may reduce the risk of cerebrovascular events during interventions that include carotid endarterectomy or stenting, coronary artery stenting, or cardiac surgery.

Školoudík and his colleagues designed SONOBIRDIE, conducted at 16 centers in Czechia, Slovakia, and Austria, to test the impact of sonolysis performed using standard ultrasound machines and 2 MHz transcranial Doppler probes during carotid endarterectomy.

The investigators randomized 1,004 patients (mean age 68 years; 31% women) with symptomatic or asymptomatic internal carotid artery stenosis ≥ 70% to either sonolysis or a sham intervention during carotid surgery; 45% of patients had symptomatic stenosis.

The rate of ischemic stroke, TIA, or death (primary composite endpoint) within the first 30 days was 2.2% among patients treated with sonolysis and 7.6% among those who received a sham intervention (risk ratio 0.28; 95% CI 0.15-0.54). There were significantly lower risks of ischemic stroke and TIA (risk ratio 0.25 and 0.23, respectively) with sonolysis, but no difference between groups in death, either at 30 days or 1 year.

Adding ultrasound was safe, too, with 94.4% of patients in that group remaining free from serious adverse events in the first 30 days. Only one patient in the trial (who received sonolysis) had intracerebral bleeding.

Further Studies Needed

In his editorial, Columbo points to some strengths of the study, including biological plausibility underpinned by prior studies of animal models and healthy adults, the use of a sham control, adjudication of outcomes by certified stroke neurologists, and supportive data from the imaging substudy.

But the high rate of adverse outcomes in the control group and the similar risk seen in patients with or without symptoms are concerns, calling “into question the internal validity of the composite outcome assessment in this study,” he writes.

Still, when considering the low risk of ultrasound, use of sonolysis during carotid endarterectomy “may be reasonable” if those questions can be resolved and cost-effectiveness can be studied, he says.

Overall, despite the issues he raised about SONOBIRDIE, Columbo said it looked like the randomization worked well, sonolysis was safe, and using ultrasound wouldn’t add much time to the procedure, though it would tie up resources when dedicating a machine and a staff member to this task.

“The risk of doing the ultrasound is really low, and this study certainly suggests that there is a benefit to doing it,” he said.

Školoudík pointed out that many centers previously used ultrasound for monitoring during carotid endarterectomy and still have the machines for other uses, so it would be easy to implement the approach studied in this trial. This “is the first step” in providing some evidence that it works, he added.