New Data on Antithrombotics in Cervical Artery Dissection
New observational data showed no significant difference in subsequent ischemic stroke with anticoagulation compared with antiplatelet therapy, although there was a nonsignificant trend toward a lower stroke rate with anticoagulation, researchers reported.
Anticoagulation therapy was not associated with a higher risk for major hemorrhage vs antiplatelet therapy at 30 days in these patients, but the difference did reach significance by 180 days.
“Our study highlights the importance of individualizing treatments in patients based on their risk of an ischemic stroke and their risk of major bleeding and trying to balance both,” Shadi Yaghi, MD, associate professor of neurology and vascular neurology chief, Brown University, Providence, Rhode Island, told Medscape Medical News.
Shadi Yaghi, MD
“One treatment really doesn’t work for all patients. When we tested anticoagulation against antiplatelet therapy, it wasn’t significant in the whole cohort, but once we started looking at subgroups that may benefit more from anticoagulation, we started seeing a difference, and one of them is occlusive dissection,” he said.
Results of the STOP-CAD study were presented at the International Stroke Conference (ISC) 2024 and published online on February 9, 2024, in Stroke.
Lack of Data
Cervical artery dissection (CAD) is not a common cause of stroke; overall, only about 2% of strokes are due to CAD. However, it accounts for about a quarter of strokes in young adults, in whom it’s a major cause of disability.
There’s not enough data from well-controlled prospective trials to help guide the use of antithrombotic treatment (anticoagulants or antiplatelet drugs) in patients with CAD. To date, there have only been two studies of note looking at this topic, and they were small and had conflicting conclusions, said Yaghi.
“This just left everyone with more questions than answers about the best treatment approach,” he said.
The current study included 3636 patients with CAD, mean age 47 years, without recent major head or neck trauma, from 63 sites in 16 countries. Of these, 11.1% received anticoagulation only, and 67.5% received antiplatelets only.
Anticoagulation therapies included therapeutic heparin or low-molecular-weight heparin, a direct oral anticoagulant, or vitamin K antagonist (VKA). Antiplatelet therapies were single agent or dual; dual therapies were mostly aspirin and clopidogrel.
Study outcomes included ischemic stroke and major hemorrhage (extracranial or symptomatic intracranial hemorrhage).
Researchers used inverse probability of treatment weighting and propensity score matching to mitigate risk for treatment bias.
The overall rates of subsequent ischemic stroke and major bleeding were low; by day 180, 4.4% of patients had a new ischemic stroke, and 0.8% had a major hemorrhage. About 87.0% of ischemic strokes occurred by day 30, and 98.1% were confirmed with imaging.
Compared to antiplatelet therapy, anticoagulation was associated with a nonsignificant lower risk for ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71; 95% CI, 0.45-1.12; P = .145) and by day 180 (adjusted HR, 0.80; 95% CI, 0.28-2.24; P = .670).
Anticoagulation therapy was not associated with a higher risk for major hemorrhage vs antiplatelets by day 30 (adjusted HR, 1.39; 95% CI, 0.35-5.45; P = .637) but it was by day 180 (adjusted HR, 5.56; 95% CI, 1.53-20.13; P = .009).
As most ischemic strokes occurred in the first 4 weeks after dissection diagnosis, a short course of a more intensive antithrombotic regimen could lower risk for stroke, said Yaghi.
Shorten Anticoagulation Duration
If anticoagulation is chosen, it’s crucial to mitigate the bleeding risk by shortening the duration of anticoagulation treatment, he added. “If you’re using anticoagulation, it’s important to consider stopping it after 30 days” or a maximum of 90 days and perhaps switch to antiplatelet therapy after that, he added.
In a preplanned adjusted interaction analysis, patients with occlusive dissection, who were at a high risk for recurrent stroke and made up about 30% of the study population, had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40; 95% CI, 0.18-0.88; P for interaction = .009) but not those with nonocclusive dissection (HR, 1.34; 95% CI, 0.83-2.14).
“These patients probably have a big blood clot that’s blocking the artery, and potentially, anticoagulation works better in this group,” said Yaghi.
It’s not clear from this study whether any particular anticoagulant regimen had a more protective effect in terms of ischemic stroke reduction as the number of patients in the different anticoagulation subgroups was too small.
Yaghi acknowledged the study doesn’t determine the optimal treatment approach for all patients with CAD. “Our study should be looked at as adding to the body of literature and not giving a definitive answer,” said Yaghi.
“Certainly with our study, we are closer to getting answers on this topic than other studies with their limitations and conflicting conclusions. Given this big dataset, it makes people more comfortable with their practice and validates what most of us do already in practice.”
Finding More Answers
The researchers are also looking to find more answers for patients with CAD. For example, they aim to compare direct oral anticoagulation with VKA, determine risk for recurrent dissection, what predicts stroke in this population, and what are the best acute treatments.
Due to the study’s retrospective and observational design, treatment bias is possible. The study also lacked central and blinded outcome adjudication, and about 10% of patients were lost to follow-up at 30 days.
Another limitation was that most study sites were at large academic institutions in high-income countries, so the findings may not be generalizable to patients treated at community hospitals or in lower-income countries. Because of low numbers, researchers were unable to reliably perform propensity score matching for the major hemorrhage outcome, and the overwhelming majority of dual antiplatelet therapies included aspirin and clopidogrel.
Commenting on the study for Medscape Medical News, Larry B. Goldstein, MD, professor and chair, Department of Neurology, and associate dean for Clinical Research, University of Kentucky, Lexington, Kentucky, said he agrees there’s a lack of well-controlled prospective trials to guide use of antithrombotic treatment in patients with CAD but doesn’t believe this new study provides additional guidance.
“Although the investigators tried to account for imbalances statistically, because treatment was not randomized, no conclusions regarding relative efficacy can be made based on these data, and the expert opinion in the recent Scientific Statement remains appropriate,” referring to the scientific statement on the topic from the American Heart Association, which recommends “antithrombotic therapy choice be individualized” based on expert opinion.
The study had no outside funding. Yaghi and Goldstein had no relevant conflicts of interest.
