Due to the number of readers of The Stroke Blog who have identified themselves as having experienced carotid or vertebral artery dissections with or without stroke, I believe a clinical trial from the United Kingdom is very much worth sharing here.
The Cervical Artery Dissection in Stroke Study (CADISS – Markus HS, et al) set out to answer a question that has existed for many decades in the world of stroke management. When a dissection (a tear in the innermost tissue layer of an artery) of a carotid artery or vertebral artery (arteries in the neck that bring blood to the brain), how is a stroke best prevented going forward? In patients who have already had a stroke at the time the dissection is diagnosed, the goal is certainly to prevent further strokes from occurring. If a patient has not already sustained a stroke, then sparing that person a permanent brain injury is the top priority. It has not been entirely clear how to achieve these goals though. Should a patient be treated with antiplatelet agents (medications impairing platelet function), such as aspirin, clopidogrel (Plavix), another antiplatelet agent, or some combination of these? Or should a patient be treated with anticoagulation, a drug that actively prevents clotting, such as warfarin (Coumadin) or heparin?
I have heard many arguments on all sides. Some neurologists say that antiplatelet therapy is just as effective as warfarin but carries a lower risk of hemorrhage. Others say that antiplatelet therapy is not aggressive enough and anticoagulation with warfarin or heparin (or both) should be used. Some say to start on antiplatelet therapy or anticoagulation and if symptoms get worse to switch to whatever therapy was not initially used. Others argue for placing a stent in the dissected artery. Until recently, there was no clinical trial actually comparing antiplatelet therapy to anticoagulation in patients with carotid artery or vertebral artery dissection, and the medicine selected for treatment was based entirely on anecdotes and the bias of the treating physician.
In the CADISS trial, patients presenting to one of the participating medical centers in the United Kingdom who were diagnosed with carotid or vertebral artery dissection (with or without stroke) believed to have occurred within the seven days prior to presentation were randomized. Half of the patients were started on antiplatelet therapy, and half were placed on anticoagulation. The duration of treatment was three months. The endpoint was to determine how many strokes or deaths occurred in each group. Whether or not the patient had already had a stroke before enrolling in the trial, the endpoint was to see, once antiplatelet therapy or anticoagulation was started, how many patients went on to have strokes despite that therapy.
Two hundred fifty patients were enrolled (118 carotid artery dissections and 132 vertebral artery dissections). Interestingly, 52 of these patients were not found to have carotid or vertebral artery dissections when their radiology studies were carefully reviewed as part of the study, despite initially receiving that diagnosis. Of the 198 patients remaining, there was no significant difference in strokes between the two groups. There was one episode of symptomatic bleeding in the anticoagulation group (subarachnoid hemorrhage, or bleeding in the brain that occurs when an artery in the brain ruptures). There were no deaths in either group. Of the 198 patients with radiological evidence of dissection confirmed, there were only four total strokes following initiation of the designated medical therapy in both groups combined.
The CADISS trial began as a feasibility study – a trial to see if it was even feasible to enroll enough patients with a condition not diagnosed with frequency in the emergency department. This phase of the study was statistically sound and convincing enough not to proceed with a larger trial.
A trial comparing stenting to medication alone has not been performed, and given the low number of strokes in patients on medical therapy in the CADISS trial, it is unlikely that a dissection stenting trial will be performed any time in the near future.
For more details about arteries bringing blood to the brain and about carotid and vertebral artery dissection, please refer to a prior post on The Stroke Blog by clicking here.
The take-away points from CADISS are as follows:
- The overwhelming majority of patients with carotid and vertebral artery dissection, if started on either antiplatelet therapy or anticoagulation soon after the dissection has occurred, will not go on to have a stroke while on therapy during the aftermath following the vascular injury.
- There is no significant difference in stroke prevention in patients with carotid and vertebral artery dissection between those using antiplatelet medications and those using anticoagulation.
The trial does not address the myriad symptoms many dissection patients notice lingering after the injury – migraines, neck pain, and anxiety, to name a few. One trial cannot address every possible issue associated with a medical condition. However, physicians who care for young stroke patients with this particular vascular injury should be celebrating the fact that we finally have evidence-based guidance for preventing stroke in these patients.