Antiplatelets, Anticoagulants Similar After Cervical Dissection

February 28, 2019

In patients with cervical dissection, there was no difference in rates of stroke, residual stenosis, or occlusion at 1 year in those treated with anticoagulants and those treated with antiplatelet agents in the CADISS trial.

The trial set out to establish whether there was a difference between the two main treatment options for cervical dissection.

The primary endpoint of the trial, which was reported in 2015, was ipsilateral stroke and death at 3 months. Results showed no difference between the two treatment groups, and there was a low rate of stroke in the trial as a whole. The 1-year results are similar.

The 1-year results are reported in an article published online February 25 in JAMA Neurology.

Given the low number of endpoints and the fact that there was no difference between the two treatment options, "it seems reasonable to treat such patients with either anticoagulants or antiplatelet agents based on the available data," the authors conclude.

The researchers, led by Hugh S. Markus, FMedSci, University of Cambridge, United Kingdom, explain that cervical dissection, a tear in the carotid or vertebral artery, is a common cause of stroke in young patients. Embolism from thrombus forming at the dissection site is thought to play the major role in stroke pathogenesis, and antithrombotic therapy is used routinely to reduce risk for stroke.

The CADISS trial is the first randomized clinical trial involving patients with carotid and vertebral dissection to compare these two treatments.

The study included 250 patients with extracranial carotid or vertebral dissection (118 carotid and 132 vertebral) in whom symptom onset occurred within the previous 7 days. Patients were randomly allocated to receive antiplatelet or anticoagulant therapy for 3 months, after which the choice of agents was made by the local clinician.

The primary endpoint at 3 months showed a low rate of recurrent stroke of 1.6% in the intention-to-treat analysis and 2.0% when only patients who met the inclusion criteria were included (per protocol).

There was no difference between event rates in patients treated with anticoagulants or antiplatelets.

One-year results — the focus of the current study — were similar. The recurrent stroke rate at 1 year was 2.4% in the intention-to-treat analysis and 2.5% in the per protocol analysis. There were no significant differences between the two treatment groups.

There were four strokes within 1 year of follow-up in the antiplatelet group and only two in the anticoagulant group, although one major hemorrhage occurred in the anticoagulant group.

Of the 181 patients with confirmed dissection who underwent complete imaging at baseline and at 3 months, there was no difference in the presence of residual narrowing or occlusion between those receiving antiplatelet agents (56 of 92) vs those receiving anticoagulants (53 of 89).

The authors note that all recurrent events occurred in patients who had presented with stroke and that none occurred in those who had presented with only local symptoms.

They point out that the recurrent stroke rate in this study was very low compared to previous studies, and they say they may have missed some early recurrent strokes prior to recruitment. Previous studies have suggested that recurrent strokes may be most frequent very early after initial stroke and transient ischemic attack.

The researchers note that CADISS was designed as a pragmatic trial, and therefore the choice of antiplatelet agent was at the clinician's discretion. Approximately 55% of patients received a single antiplatelet agent, either clopidogrel (Plavix, Sanofi-Aventis) or aspirin, and 45% received dual antiplatelet therapy.

They point out that increasing evidence suggests that the combination of aspirin and clopidogrel may be more effective in preventing early recurrent strokes in patients with atherosclerotic large-artery stenosis, and it is possible that antiplatelet therapy may have been more effective had all patients been given this combination.

Patients who received anticoagulation therapy were given heparin then warfarin because CADISS started before novel oral anticoagulants were introduced. The authors state that although this trial cannot give information on the effectiveness of the new oral anticoagulants compared with antiplatelets in preventing stroke after dissection, they note that data on stroke prevention in general suggest they are roughly equivalent in efficacy to warfarin.

The CADISS study was supported by a project grant from the Stroke Association. The authors report no relevant financial relationships.

JAMA Neurol. Published online February 25, 2019. Abstract

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