Pierre Amarenco1, Stephen Davis, Elizabeth F Jones, Ariel A Cohen, Wolf-Dieter Heiss, Markku Kaste, Cédric Laouénan, Dennis Young, Malcolm Macleod, Geoffrey A Donnan. 1. From the Department of Neurology, Stroke Centre, DHU FIRE, INSERM U 1148, Paris Diderot-Sorbonne University, Hôpital Bichat (P.A.), Department of Cardiology, Saint-Antoine Hospital and Medical School, Univeristé Pierre et Marie Curie (A.A.C.), and Department of Biostatistics, Paris-Diderot-Sorbonne University, Hôpital Bichat (C.L.), Assistance Publique-Hôpitaux de Paris, Paris, France; Department of Neurology, Royal Melbourne Hospital (S.D.) and Florey Institute of Neuroscience and Mental Health (D.Y., M.M., G.A.D.), University of Melbourne, Melbourne, Australia; Department of Cardiology, Austin Health, Heidelberg, Victoria, Australia (E.F.J.); Max Planck Institute for Neurological Research, Cologne, Germany (W.-D.H.); Department of Neurology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland (M.K.); Stroke and Ageing Research Centre, Monash University, Melbourne, Australia (D.Y.); and Division of Clinical Neurosciences, University of Edinburgh (SC005336), Scotland, United Kingdom (M.M.).
Abstract
BACKGROUND AND PURPOSE: Severe atherosclerosis in the aortic arch is associated with a high risk of recurrent vascular events, but the optimal antithrombotic strategy is unclear. METHODS: This prospective randomized controlled, open-labeled trial, with blinded end point evaluation (PROBE design) tested superiority of aspirin 75 to 150 mg/d plus clopidogrel 75 mg/d (A+C) over warfarin therapy (international normalized ratio 2-3) in patients with ischemic stroke, transient ischemic attack, or peripheral embolism with plaque in the thoracic aorta>4 mm and no other identified embolic source. The primary end point included cerebral infarction, myocardial infarction, peripheral embolism, vascular death, or intracranial hemorrhage. Follow-up visits occurred at 1 month and then every 4 months post randomization. RESULTS: The trial was stopped after 349 patients were randomized during a period of 8 years and 3 months. After a median follow-up of 3.4 years, the primary end point occurred in 7.6% (13/172) and 11.3% (20/177) of patients on A+C and on warfarin, respectively (log-rank, P=0.2). The adjusted hazard ratio was 0.76 (95% confidence interval, 0.36-1.61; P=0.5). Major hemorrhages including intracranial hemorrhages occurred in 4 and 6 patients in the A+C and warfarin groups, respectively. Vascular deaths occurred in 0 patients in A+C arm compared with 6 (3.4%) patients in the warfarin arm (log-rank, P=0.013). Time in therapeutic range (67% of the time for international normalized ratio 2-3) analysis by tertiles showed no significant differences across groups. CONCLUSIONS: Because of lack of power, this trial was inconclusive and results should be taken as hypothesis generating. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00235248.
RCT Entities:
BACKGROUND AND PURPOSE: Severe atherosclerosis in the aortic arch is associated with a high risk of recurrent vascular events, but the optimal antithrombotic strategy is unclear. METHODS: This prospective randomized controlled, open-labeled trial, with blinded end point evaluation (PROBE design) tested superiority of aspirin 75 to 150 mg/d plus clopidogrel 75 mg/d (A+C) over warfarin therapy (international normalized ratio 2-3) in patients with ischemic stroke, transient ischemic attack, or peripheral embolism with plaque in the thoracic aorta>4 mm and no other identified embolic source. The primary end point included cerebral infarction, myocardial infarction, peripheral embolism, vascular death, or intracranial hemorrhage. Follow-up visits occurred at 1 month and then every 4 months post randomization. RESULTS: The trial was stopped after 349 patients were randomized during a period of 8 years and 3 months. After a median follow-up of 3.4 years, the primary end point occurred in 7.6% (13/172) and 11.3% (20/177) of patients on A+C and on warfarin, respectively (log-rank, P=0.2). The adjusted hazard ratio was 0.76 (95% confidence interval, 0.36-1.61; P=0.5). Major hemorrhages including intracranial hemorrhages occurred in 4 and 6 patients in the A+C and warfarin groups, respectively. Vascular deaths occurred in 0 patients in A+C arm compared with 6 (3.4%) patients in the warfarin arm (log-rank, P=0.013). Time in therapeutic range (67% of the time for international normalized ratio 2-3) analysis by tertiles showed no significant differences across groups. CONCLUSIONS: Because of lack of power, this trial was inconclusive and results should be taken as hypothesis generating. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00235248.
Authors: Victor J Del Brutto; Seemant Chaturvedi; Hans-Christoph Diener; Jose G Romano; Ralph L Sacco Journal: J Am Coll Cardiol Date: 2019-08-13 Impact factor: 24.094
Authors: Hebun Erdur; Lennart S Milles; Jan F Scheitz; Kersten Villringer; Karl Georg Haeusler; Matthias Endres; Heinrich J Audebert; Jochen B Fiebach; Christian H Nolte Journal: Eur Radiol Date: 2018-08-23 Impact factor: 5.315