Clopidogrel plus aspirin versus warfarin in patients with stroke and aortic arch plaques
Pierre Amarenco, Stephen Davis, Elizabeth F Jones, Ariel A Cohen, Wolf-Dieter Heiss, Markku Kaste, Cédric Laouénan, Dennis Young, Malcolm Macleod, Geoffrey A Donnan, Aortic Arch Related Cerebral Hazard Trial Investigators, Christopher F Bladin, Brian R Chambers, Judith Frayne, Graeme J Hankey, Christopher R Levi, Stephen J Read, Philippe Ravaud, Turgut Tatlisumak, Lauri Soinne, Mika Laine, Mikko Syvänne, Pirkka Vikatmaa, Mauri Lepäntalo, France Mentré, Simon Gosset, Leonid Churilov, Thomas De Broucker, Pascal Favrole, Jérôme Mawet, Yves Mocquard, Michael Obadia, Olivier Godefroy, Hassan Hosseini, Fernando Pico, Pierre Garnier, Marcel Malbec, Jean-François Pinel, Olivier Ille, Xavier Vadamme, Francisco Macian-Montoro, Jérôme Servan, François Viallet, Thierry Rosolacci, Patrick Lecoz, Pierre Clavelou, Olivier Detante, Tae-Hee Cho, Denis Saudeau, Patrik Michel, Suzette D'Ombrogio, David Serisier, Jonathon Sturm, Thomas Kimber, Romesh Marcus, Ray Schwartz, Rob Helme, David Blacker, Jonathan Wood, Pierre Amarenco, Stephen Davis, Elizabeth F Jones, Ariel A Cohen, Wolf-Dieter Heiss, Markku Kaste, Cédric Laouénan, Dennis Young, Malcolm Macleod, Geoffrey A Donnan, Aortic Arch Related Cerebral Hazard Trial Investigators, Christopher F Bladin, Brian R Chambers, Judith Frayne, Graeme J Hankey, Christopher R Levi, Stephen J Read, Philippe Ravaud, Turgut Tatlisumak, Lauri Soinne, Mika Laine, Mikko Syvänne, Pirkka Vikatmaa, Mauri Lepäntalo, France Mentré, Simon Gosset, Leonid Churilov, Thomas De Broucker, Pascal Favrole, Jérôme Mawet, Yves Mocquard, Michael Obadia, Olivier Godefroy, Hassan Hosseini, Fernando Pico, Pierre Garnier, Marcel Malbec, Jean-François Pinel, Olivier Ille, Xavier Vadamme, Francisco Macian-Montoro, Jérôme Servan, François Viallet, Thierry Rosolacci, Patrick Lecoz, Pierre Clavelou, Olivier Detante, Tae-Hee Cho, Denis Saudeau, Patrik Michel, Suzette D'Ombrogio, David Serisier, Jonathon Sturm, Thomas Kimber, Romesh Marcus, Ray Schwartz, Rob Helme, David Blacker, Jonathan Wood
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.
Keywords: aorta; atherosclerosis; cerebral infarction.
Source: PubMed