Three New Trials in Stroke: CADISS, VISSIT, and ATTEST
Three New Trials in Stroke: CADISS, VISSIT, and ATTEST
I am Christoph Diener, a neurologist from the University of Essen in Germany. Today I would like to report the results of three randomized controlled trials which were published in the April issues of JAMA and Lancet Neurology.
The first trial is the Cervical Artery Dissection in Stroke Study (CADISS). This trial investigated whether secondary prevention should be performed with either anticoagulation or with antiplatelet therapy in patients who have had dissection of the internal carotid artery or vertebral artery. Investigators recruited 250 patients, 118 with dissection of the internal carotid artery and 132 with dissection of the vertebral artery. Most of these dissections were asymptomatic. Patients were then randomized within 7 days to receive either oral anticoagulation, initially with heparin followed by warfarin, or antiplatelet therapy (with the specific treatment decided by the treating physician). During 1-year follow-up, four patients had recurrent stroke. I think the study showed two very importantly things. The recurrent stroke rate in dissection was extremely low and there was no difference in recurrence rate between anticoagulation and antiplatelet therapy. Therefore, I think it is safe to use antiplatelet therapy in these patients. What we don't know is whether the new oral anticoagulants would perform better than warfarin in this situation.
The second trial, the Vitesse Intracranial Stent Study for Ischemic Stroke Therapy (VISSIT), was conducted in patients with symptomatic intracranial stenosis. We have already had the SAMMPRIS trial, which was clearly negative for stent placement, and this trial was stopped at the time when SAMMPRIS was published and follow-up was done. VISSIT randomized 112 patients with symptomatic intracranial stenosis to receive balloon angioplasty and stenting or best medical therapy alone. The trial was clearly negative for the stenting group. The primary safety endpoint, which was stroke, death, or intracranial hemorrhage within 30 days, occurred in 24% of patients in the stenting group and 9% of patients in the medical therapy group. The rate of stroke and transient ischemic attack at 1 year was 36% in the stenting group vs 15% in the best medical treatment group. We now have two trials that clearly indicate that stenting of symptomatic intracranial stenosis is inferior to best medical treatment. What we don't know is what happens to patients who have recurrent ischemic events on optimal medical therapy. This was not tested in these two trials (VISSIT and SAMMPRIS).
The third trial is the Alteplase-Tenecteplase Trial Evaluation for Thrombolysis (ATTEST). We have two drugs for systemic thrombolysis in acute ischemic stroke: the approved recombinant tissue plasminogen activator (rtPA) alteplase, and tenecteplase. Tenecteplase is given in a bolus, and in a phase 2 study from Australia, which was a dose-finding study, it seemed to be superior to rtPA alteplase. The present study was done in Scotland and included 104 patients with acute ischemic stroke who were randomized to receive either tenecteplase or alteplase. The investigators used a surrogate parameter of efficacy. They performed diffusion rate imaging immediately before treatment in order to identify penumbra. Subsequently, they performed CT 24-48 hours later to determine the size of the final infarct and subtracted this from the initial lesion seen on perfusion CT. This study showed no difference between the two treatments. The size of infarcts was identical, and overall this study was too small to detect a clinical benefit. In contrast to the phase 2 study from Australia, this study did not indicate that tenecteplase was superior to alteplase. Therefore, we should stick to alteplase, the only proven medical treatment for acute ischemic stroke in a 4.5-hour window.
Lots of exciting things are happening in stroke, and today we had three new trials on dissection in intracranial stenosis and on thrombolysis in acute ischemic stroke. Thank you very much for watching. I am Christoph Diener, a neurologist from the University of Essen in Germany.
I am Christoph Diener, a neurologist from the University of Essen in Germany. Today I would like to report the results of three randomized controlled trials which were published in the April issues of JAMA and Lancet Neurology.
The first trial is the Cervical Artery Dissection in Stroke Study (CADISS). This trial investigated whether secondary prevention should be performed with either anticoagulation or with antiplatelet therapy in patients who have had dissection of the internal carotid artery or vertebral artery. Investigators recruited 250 patients, 118 with dissection of the internal carotid artery and 132 with dissection of the vertebral artery. Most of these dissections were asymptomatic. Patients were then randomized within 7 days to receive either oral anticoagulation, initially with heparin followed by warfarin, or antiplatelet therapy (with the specific treatment decided by the treating physician). During 1-year follow-up, four patients had recurrent stroke. I think the study showed two very importantly things. The recurrent stroke rate in dissection was extremely low and there was no difference in recurrence rate between anticoagulation and antiplatelet therapy. Therefore, I think it is safe to use antiplatelet therapy in these patients. What we don't know is whether the new oral anticoagulants would perform better than warfarin in this situation.
The second trial, the Vitesse Intracranial Stent Study for Ischemic Stroke Therapy (VISSIT), was conducted in patients with symptomatic intracranial stenosis. We have already had the SAMMPRIS trial, which was clearly negative for stent placement, and this trial was stopped at the time when SAMMPRIS was published and follow-up was done. VISSIT randomized 112 patients with symptomatic intracranial stenosis to receive balloon angioplasty and stenting or best medical therapy alone. The trial was clearly negative for the stenting group. The primary safety endpoint, which was stroke, death, or intracranial hemorrhage within 30 days, occurred in 24% of patients in the stenting group and 9% of patients in the medical therapy group. The rate of stroke and transient ischemic attack at 1 year was 36% in the stenting group vs 15% in the best medical treatment group. We now have two trials that clearly indicate that stenting of symptomatic intracranial stenosis is inferior to best medical treatment. What we don't know is what happens to patients who have recurrent ischemic events on optimal medical therapy. This was not tested in these two trials (VISSIT and SAMMPRIS).
The third trial is the Alteplase-Tenecteplase Trial Evaluation for Thrombolysis (ATTEST). We have two drugs for systemic thrombolysis in acute ischemic stroke: the approved recombinant tissue plasminogen activator (rtPA) alteplase, and tenecteplase. Tenecteplase is given in a bolus, and in a phase 2 study from Australia, which was a dose-finding study, it seemed to be superior to rtPA alteplase. The present study was done in Scotland and included 104 patients with acute ischemic stroke who were randomized to receive either tenecteplase or alteplase. The investigators used a surrogate parameter of efficacy. They performed diffusion rate imaging immediately before treatment in order to identify penumbra. Subsequently, they performed CT 24-48 hours later to determine the size of the final infarct and subtracted this from the initial lesion seen on perfusion CT. This study showed no difference between the two treatments. The size of infarcts was identical, and overall this study was too small to detect a clinical benefit. In contrast to the phase 2 study from Australia, this study did not indicate that tenecteplase was superior to alteplase. Therefore, we should stick to alteplase, the only proven medical treatment for acute ischemic stroke in a 4.5-hour window.
Lots of exciting things are happening in stroke, and today we had three new trials on dissection in intracranial stenosis and on thrombolysis in acute ischemic stroke. Thank you very much for watching. I am Christoph Diener, a neurologist from the University of Essen in Germany.
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