Ticagrelor May Reduce Brain Lesions After Carotid Stenting

MUNICH — Patients undergoing carotid artery stenting (CAS) may have fewer ischemic lesions and a lower lesion burden if they are given the reversible P2Y12 receptor antagonist ticagrelor rather than clopidogrel, another P2Y12 inhibitor, prior to the procedure, secondary endpoint results of the PRECISE-MRI trial suggest.

More than 200 patients with carotid artery stenosis underwent magnetic resonance imaging (MRI) and were randomized to ticagrelor or clopidogrel before undergoing CAS. They then had two follow-up MRIs to assess the presence of emergent ischemic lesions.

Although the trial, which was stopped early, failed to show a difference between the two treatments in the primary endpoint — occurrence of at least one ischemic lesion — it did show that ticagrelor was associated with significant reductions in secondary endpoints including the total number and total volume of new lesions.

There were also significantly fewer cases of a composite of adverse clinical events with ticagrelor versus clopidogrel, but no difference in rates of hemorrhagic bleeds.

The research was presented at the 9th European Stroke Organisation Conference (ESOC) 2023 on May 25.

Highlighting the failure of the trial to meet its primary endpoint, study presenter Leo Bonati, MD, head of the Stroke Center, Rena Rheinfelden, University Hospital Basel, Switzerland, pointed out that the proportion of patients with one or more ischemic brain lesions was “much higher than expected.”

Based on the secondary outcomes, the study nevertheless indicates that, “compared with clopidogrel, ticagrelor reduces the total burden of ischemic brain lesions occurring during CAS,” he said.

Ticagrelor is therefore a “safe alternative to clopidogrel as an add-on to aspirin to cover carotid artery stent procedures.”

Bonati cautioned, however, that the findings are preliminary.

“Promising” Results

Session cochair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the Stroke Unit, Department of Neurology, Oslo University Hospital, Norway, called the results “interesting” and “promising.”

She told Medscape Medical News that they “also provide us with an additional option” in the management of patients undergoing CAS.

Sandset suggested that “it may have been a little bit hard to prove the primary endpoint” chosen for the trial, but believes that the secondary endpoint results “are very interesting.”

“Of course, we would need more data and further trials to provide some reassurance that we can use ticagrelor in this fashion,” she said.

Major Complication

Bonati began by noting that the major procedural complication of CAS is embolic stroke, but this may be prevented with optimized antiplatelet therapy.

Previous studies have shown that ticagrelor is superior to clopidogrel as an add-on to aspirin in reducing rates of major adverse cardiovascular events in acute coronary syndrome patients undergoing percutaneous coronary intervention.

Adding the drug to aspirin is also superior to aspirin alone in preventing recurrent stroke in patients with minor stroke or transient ischemic attack, Bonati said.

To examine whether ticagrelor is superior to clopidogrel as an add-on to aspirin in preventing ischemic brain lesions during CAS, the team conducted a randomized, open, active-controlled trial.

They recruited patients with ≥ 50% symptomatic or asymptomatic carotid stenosis undergoing CAS in line with local guidelines and performed a baseline MRI scan and clinical examination.

The patients were then randomized to ticagrelor or clopidogrel plus aspirin 1 to 3 days before undergoing CAS. A second MRI and clinical examination, as well as an ultrasound scan, was performed at 1 to 3 days post-CAS, with a third set of examinations performed at 28 to 32 days after the procedure.

The study included 14 sites in Belgium, Germany, Italy, the Netherlands, Switzerland, and the United Kingdom. Enrollment was stopped after 209 of the originally planned 370 patients, “due to slow recruitment and a lack of further funding,” Bonati said.

Of those, 207 patients were included in the intention-to-treat safety analysis, and 172 in the per-protocol efficacy analysis.

The mean age of the patients was 69.0 – 69.5 years in the two treatment groups, and 67% – 71% were male. Bonati noted that 52% – 55% of the patients had symptomatic stenosis, and that in 83% – 88% the stenosis was severe.

The majority (79% – 82%) of patients had hypertension, alongside hypercholesterolemia, at 76% in both treatment groups.

Bonati showed that there was no significant difference in the primary efficacy outcome of the presence of ≥ 1 new ischemic brain lesion on the second or third MRI, at 74.7% for patients given ticagrelor versus 79.8% with clopidogrel, or a relative risk of 0.94 (95% confidence interval [CI], 0.79 – 1.10; P = .43).

However, there was a significant reduction in the number of new ischemic lesions, at a median of 2 (interquartile range [IQR] 0.5 – 5.5) with ticagrelor versus 3 with clopidogrel (IQR 1 – 8), or an exponential beta value of 0.63 (95% CI, 0.42 – 0.95; P = .027).

Ticagrelor was also associated with a significant reduction in the total volume of lesions, at a median of 66 µl (IQR 2.5 – 2.19) versus 91 µl (IQR 25 – 394) for clopidogrel, or an exponential beta value of 0.30 (95% CI, 0.10 – 0.92; P = .030).

Patients assigned to ticagrelor also had a significantly lower rate of the primary clinical safety outcome, a composite of stroke, myocardial infarction, major bleeding, or cardiovascular death, at 2.9% versus 7.8%, or a relative risk of 0.36 (95% CI, 0.08 – 1.20). This was driven by a reduction in rates of post-CAS stroke.

Bonati noted that there was no significant difference in the presence of ≥ 1 hemorrhagic lesion after CAS, at 42.7% with ticagrelor and 47.6% in the clopidogrel group, or a relative risk of 0.90 (95% CI, 0.63 – 1.26).

There was also a similar rate of microbleeds between the two treatment groups, at 36.6% in patients given ticagrelor and 47.6% in those assigned to clopidogrel.

European Stroke Organisation Conference (ESOC) 2023: Abstract 658. Presented May 25.

The study was investigator-initiated and funded by an unrestricted research grant from AstraZeneca. No relevant financial relationships declared.