Preventing Stroke After Cervical Artery Dissection

Antiplatelet or anticoagulant treatment performed equally well in preventing strokes in cervical artery dissection patients at 1 year, final results of the open-label CADISS clinical trial showed.

The number of recurrent strokes was low — 2.4% on intention-to-treat analysis and 2.5% on per protocol — and there were no significant differences between antiplatelet treatment and anticoagulant treatment for any outcome at 1 year, reported Hugh Markus, FMedSci, of the University of Cambridge in England, and co-authors in JAMA Neurology.

There was no difference in residual narrowing or occlusion between the treatment groups at 3 months, they added.

Cervical artery dissection begins as a tear in a carotid or vertebral artery in the neck, causing blood to leak and spread between layers of the arterial wall. The condition is rare, accounting for 1-2% of all ischemic strokes, but is a common cause of stroke in young patients.

Some studies have suggested that cervical artery dissection patients have a high risk for secondary stroke, with embolism from thrombus forming at the dissection site perhaps playing a major role. Both antiplatelet and anticoagulant drugs often are used to reduce embolization risk.

CADISS (Cervical Artery Dissection in Stroke Study) provided the first randomized clinical trial data about carotid and vertebral dissection. In 2015, the trial’s 3-month results showed a low rate of recurrent stroke — 2% on per protocol analysis (when patients who did not have confirmed diagnosis on central imaging review were excluded) — with no significant differences between antiplatelet and anticoagulant treatment.

From 2006 to 2013, CADISS researchers recruited 250 patients from 39 centers in the U.K. and seven centers in Australia with extracranial carotid and vertebral dissection who had symptom onset within the last 7 days. Most patients presented with cerebral ischemia (194 ischemic stroke, one retinal infarction, and 29 transient ischemic attack), and 26 patients presented with local symptoms (22 headache and neck pain, and four Horner syndrome). Of the total sample, 198 patients had radiologically confirmed dissection.

Patients were randomized 1:1 to either antiplatelet or anticoagulation therapy for at least 3 months, with drug choice left to local physicians. Antiplatelet therapy could be aspirin, clopidogrel (Plavix), or dipyridamole (Persantine), or dual combination. Anticoagulant treatment was heparin followed by warfarin (Coumadin). After 3 months, antithrombotic treatment was the choice of the treating clinician.

Mean age of patients in the trial was 49 years; 118 had carotid dissection and 132 had vertebral. Mean time to randomization was 3.65 days.

During the first 3 months, there were four recurrent strokes, all ipsilateral, and no deaths. From 3 to 12 months, there were two further strokes, both ipsilateral, and one death that occurred in a patient who had experienced recurrent stroke in the first 3 months. All recurrent events occurred in patients who had presented with stroke and none occurred in those presenting with only local symptoms.

At 1 year, there were four events in the antiplatelet arm and three in the anticoagulation arm for the combined end point of stroke, death, or major bleeding.

Of 181 patients with confirmed dissection and complete imaging at baseline and 3 months, there was no difference in residual narrowing or occlusion between the antiplatelet group (56 of 92 patients) versus the anticoagulant group (53 of 89 patients; P=0.97).

“Our results demonstrate that not only was the early risk of stroke lower than that reported in some previous studies, many of which were based on retrospective analysis with incomplete follow-up, but the later risk of recurrence between 3 and 12 months was also very low, with only two additional strokes in the 250 patients; of these, one was in each treatment arm,” Markus and colleagues noted.

The low number of end points means that a very large sample size — many thousands — would be needed to detect differences between the two treatment strategies, and the absolute effect would be very low, they pointed out: “Therefore, it seems reasonable to treat such patients with either anticoagulation or antiplatelet agents based on the available data.”

About 55% of patients in the antiplatelet group received a single agent (either clopidogrel or aspirin) and 45% received dual treatment. It is possible antiplatelet treatment would have been more effective if all patients received a combination of aspirin and clopidogrel, the authors noted. All patients in the anticoagulation group received warfarin because the trial started before novel oral anticoagulants were available, the researchers explained. In addition, the trial may have missed some early recurrent strokes before patients were recruited, and there were also imaging limitations: dissection diagnosis could not be confirmed radiographically in about 20% of patients.