Titre du document / Document title

Magnitude and time course of platelet inhibition with Aggrenox® and Aspirin in patients after ischemic stroke: the AGgrenox versus Aspirin Therapy Evaluation (AGATE) trial

Auteur(s) / Author(s)

SEREBRUANY Victor L. ⁽¹⁾ ; MALININ Alex I. ⁽¹⁾ ; SANE David C. ⁽²⁾ ; JILMA Bernd ⁽³⁾ ; TAKSERMAN Aviv ⁽⁴⁾ ; ATAR Dan ⁽⁴⁾ ; HENNEKENS Charles H. ⁽⁵⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ HeartDrug Research Laboratories, 7600 Osler Drive, Ste. 307, Towson, MD 21204, ETATS-UNIS
⁽²⁾ Wake Forest University, 1834 Wake Forest Road, Winston-Salem, NC 27106, ETATS-UNIS
⁽³⁾ Medical University of Vienna, Wahringer Cartel 18-20, Vienna, 1090, AUTRICHE
⁽⁴⁾ Aker University Hospital, Division of Cardiology Trondheimsyn, 235, Oslo, 0514, NORVEGE
⁽⁵⁾ Miami Heart Institute, 4300 Alton Road, Miami Beach, FL 33140, ETATS-UNIS

Résumé / Abstract

The European Stroke Prevention Study showed greater stroke prevention for Aggrenox ® than either for aspirin or dipyridamole alone. To test whether Aggrenox® has superior antiplatelet properties to aspirin alone we conducted the AGgrenox versus Aspirin Therapy Evaluation (AGATE) trial. Forty patients with prior ischemic stroke not taking aspirin for at least 30 days were randomized to Aggrenox® (2 pills/daily) or aspirin (81 mg plus matching placebo/daily) for 30 days. Platelet function was assessed at baseline, 24 h, and days 3, 7, 15, and 30 by aggregometry, flow cytometry and cartridge-based analyzers. Both Aggrenox® and aspirin provided fast and sustained platelet inhibition. Aggrenox®, however, especially after 15 days, showed significant prolongation of the closure time (P=0.04), diminished expression of platelet/endothelial cell adhesion molecule-1 (PECAM-1) (P=0.01), glycoprotein IIb (GPIIb) antigen (P=0.02), and GPIIb/IIIa activity (P=0.01) by PAC-1 C antibody, CD63 (P=0.03), as well as inhibition of Protease Activated Receptors (PAR-1) associated with intact (SPAN12, P=0.01) and cleaved (WEDE15, P=0.01) thrombin receptors as compared with aspirin. Surprisingly, GPIb expression increased, especially after aspirin. In the randomized trial of small sample size, aspirin and Aggrenox® produced fast and sustained platelet inhibition. In 25 of 90 direct comparisons, Aggrenox® was superior to aspirin, whereas in 4 of 90, aspirin was superior to Aggrenox®. In 61 of 90 direct comparisons, aspirin and Aggrenox® were equivalent. Aggrenox® was associated with a profound reduction of PAR-1 receptors, an observation that may be related to the greater clinical benefit of Aggrenox® compared with Aspirin in preventing recurrent stroke.

Revue / Journal Title

European journal of pharmacology   ISSN 0014-2999   CODEN EJPHAZ 

Source / Source

2004, vol. 499, n^o3, pp. 315-324 [10 page(s) (article)] (1 p.1/4)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Amsterdam, PAYS-BAS  (1967) (Revue)

Mots-clés anglais / English Keywords

Vascular disease ; Nervous system diseases ; Central nervous system disease ; Cerebral disorder ; Cerebrovascular disease ; Cardiovascular disease ; Salicylates ; Enzyme ; Oxidoreductases ; Prostaglandin-endoperoxide synthase ; Enzyme inhibitor ; Antiplatelet agent ; Non steroidal antiinflammatory agent ; Analgesic ; Antipyretic ; Randomization ; Treatment ; Comparative study ; Stroke ; Ischemia ; Human ; Acetylsalicylic acid ; Platelet ;

Mots-clés français / French Keywords

Vaisseau sanguin pathologie ; Système nerveux pathologie ; Système nerveux central pathologie ; Encéphale pathologie ; Cérébrovasculaire pathologie ; Appareil circulatoire pathologie ; Salicylés ; Enzyme ; Oxidoreductases ; Prostaglandin-endoperoxide synthase ; Inhibiteur enzyme ; Inhibiteur thromboagrégation ; Antiinflammatoire non stéroïde ; Analgésique ; Antipyrétique ; Randomisation ; Traitement ; Etude comparative ; Accident cérébrovasculaire ; Ischémie ; Homme ; Acétylsalicylique acide ; Thrombocyte ;

Mots-clés espagnols / Spanish Keywords

Vaso sanguíneo patología ; Sistema nervioso patología ; Sistema nervosio central patología ; Encéfalo patología ; Vaso sanguíneo encéfalo patología ; Aparato circulatorio patología ; Salicilatos ; Enzima ; Oxidoreductases ; Prostaglandin-endoperoxide synthase ; Inhibidor enzima ; Inhibidor tromboagregación ; Antiinflamatorio no esteroide ; Analgésico ; Antipirético ; Aleatorización ; Tratamiento ; Estudio comparativo ; Accidente cerebrovascular ; Isquemia ; Hombre ; Acetilsalicilico ácido ; Trombocito ;

Mots-clés d'auteur / Author Keywords

Randomized trial ; Aspirin ; Aggrenox® ; Platelet ; Stroke ;

Localisation / Location

INIST-CNRS, Cote INIST : 13322, 35400012043700.0120