Clopidogrel plus aspirin versus warfarin in patients with stroke and aortic arch plaques.
OBJECTIVE
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.


BACKGROUND
http://www.clinicaltrials.gov. Unique identifier: NCT00235248.
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.).
Pierre
P
Amarenco
Stephen
S
Davis
Elizabeth F
EF
Jones
Ariel A
AA
Cohen
Wolf-Dieter
WD
Heiss
Markku
M
Kaste
Cédric
C
Laouénan
Dennis
D
Young
Malcolm
M
Macleod
Geoffrey A
GA
Donnan
D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000473:pathology; D001018:Aortic Diseases / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D002545:Brain Ischemia / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D004617:Embolism / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011446:Prospective Studies; D016037:Single-Blind Method; D020521:Stroke / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage / Q000494:pharmacology*
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D014859:Warfarin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
aorta; atherosclerosis; cerebral infarction