Hugh S Markus1, Susanna C Larsson1, John Dennis2, Wilhelm Kuker3, Ursula G Schulz3, Ian Ford4, Andrew Clifton5, Peter M Rothwell3. 1. Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. 2. Patient representative, London, UK. 3. Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK. 4. Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK. 5. Department of Neuroradiology, St George's Hospital, London, UK.
Abstract
BACKGROUND:Symptomatic vertebral artery (VA) stenosis has been associated with a markedly increased early risk of recurrent stroke. VA stenosis can be treated with stenting; however, there are few data from randomised controlled trials evaluating the efficacy of this treatment, and recent studies in intracranial stenosis have suggested that stenting may be associated with increased risk. OBJECTIVE: The Vertebral artery Ischaemia Stenting Trial (VIST) was established to compare the risks and benefits of vertebral angioplasty and stenting with best medical treatment (BMT) alone for recently symptomatic VA stenosis. DESIGN:VIST was a prospective, randomised, open, parallel, blinded end-point clinical trial. SETTING: The trial was performed in 14 hospitals in the UK. PARTICIPANTS: Recruitment began on 23 October 2008 and follow-up ended on 1 March 2016, by which time every patient had been followed up for at least 1 year. Participants had to have symptomatic vertebral stenosis of at least 50% resulting from presumed atheromatous disease. Both patients and clinicians were aware of treatment allocation; however, an independent adjudication committee, masked to treatment allocation, assessed all primary and secondary end points. INTERVENTIONS: Participants were randomly assigned (1 : 1) to either vertebral angioplasty/stenting plus BMT (n = 91) or BMT alone (n = 88). A total of 182 patients were initially enrolled; however, three patients (two who withdrew after randomisation and one who did not attend after the initial randomisation visit) did not contribute any follow-up data and were excluded. None of these three patients had outcome events. MAIN OUTCOMES AND MEASURES: The primary end point was the occurrence of fatal or non-fatal stroke in any arterial territory during follow-up. RESULTS: The median follow-up was 3.5 (interquartile range 2.1-4.7) years. Of the 61 patients who were stented, 48 (78.7%) had extracranial stenosis and 13 (21.3%) had intracranial stenosis. No perioperative complications occurred with extracranial stenting; two strokes occurred during intracranial stenting. The primary end point occurred in five patients (including one fatal stroke) in the stent group and in 12 patients (including two fatal strokes) in the medical group (giving a hazard ratio of 0.40, 95% confidence interval 0.14 to 1.13; p = 0.08), with an absolute risk reduction of 25 strokes per 1000 person-years. LIMITATIONS: The study was underpowered because it failed to reach target recruitment. The high rate of non-confirmation of stenosis in the stented group of the trial was a second limitation. CONCLUSIONS: The trial found no difference in risk of the primary end point between the two groups. FUTURE: Post hoc analysis suggested that stenting could be associated with a reduced recurrent stroke risk in symptomatic VA and further studies are now required to confirm these findings, particularly in extracranial VA stenosis where complication rates with stenting were confirmed to be very low. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95212240. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 41. See the NIHR Journals Library website for further project information. In addition, funding for the pilot phase was provided by the Stroke Association.
RCT Entities:
BACKGROUND: Symptomatic vertebral artery (VA) stenosis has been associated with a markedly increased early risk of recurrent stroke. VA stenosis can be treated with stenting; however, there are few data from randomised controlled trials evaluating the efficacy of this treatment, and recent studies in intracranial stenosis have suggested that stenting may be associated with increased risk. OBJECTIVE: The Vertebral artery Ischaemia Stenting Trial (VIST) was established to compare the risks and benefits of vertebral angioplasty and stenting with best medical treatment (BMT) alone for recently symptomatic VA stenosis. DESIGN: VIST was a prospective, randomised, open, parallel, blinded end-point clinical trial. SETTING: The trial was performed in 14 hospitals in the UK. PARTICIPANTS: Recruitment began on 23 October 2008 and follow-up ended on 1 March 2016, by which time every patient had been followed up for at least 1 year. Participants had to have symptomatic vertebral stenosis of at least 50% resulting from presumed atheromatous disease. Both patients and clinicians were aware of treatment allocation; however, an independent adjudication committee, masked to treatment allocation, assessed all primary and secondary end points. INTERVENTIONS:Participants were randomly assigned (1 : 1) to either vertebral angioplasty/stenting plus BMT (n = 91) or BMT alone (n = 88). A total of 182 patients were initially enrolled; however, three patients (two who withdrew after randomisation and one who did not attend after the initial randomisation visit) did not contribute any follow-up data and were excluded. None of these three patients had outcome events. MAIN OUTCOMES AND MEASURES: The primary end point was the occurrence of fatal or non-fatal stroke in any arterial territory during follow-up. RESULTS: The median follow-up was 3.5 (interquartile range 2.1-4.7) years. Of the 61 patients who were stented, 48 (78.7%) had extracranial stenosis and 13 (21.3%) had intracranial stenosis. No perioperative complications occurred with extracranial stenting; two strokes occurred during intracranial stenting. The primary end point occurred in five patients (including one fatal stroke) in the stent group and in 12 patients (including two fatal strokes) in the medical group (giving a hazard ratio of 0.40, 95% confidence interval 0.14 to 1.13; p = 0.08), with an absolute risk reduction of 25 strokes per 1000 person-years. LIMITATIONS: The study was underpowered because it failed to reach target recruitment. The high rate of non-confirmation of stenosis in the stented group of the trial was a second limitation. CONCLUSIONS: The trial found no difference in risk of the primary end point between the two groups. FUTURE: Post hoc analysis suggested that stenting could be associated with a reduced recurrent stroke risk in symptomatic VA and further studies are now required to confirm these findings, particularly in extracranial VA stenosis where complication rates with stenting were confirmed to be very low. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95212240. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 41. See the NIHR Journals Library website for further project information. In addition, funding for the pilot phase was provided by the Stroke Association.