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.
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(R), 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.
authors.affiliation: HeartDrug Research Laboratories, 7600 Osler Drive, Ste. 307, Towson, MD 21204, USA. heartdrug@aol.com
authors.forename: Victor L
authors.initials: VL
authors.lastname: Serebruany
authors.forename: Alex I
authors.initials: AI
authors.lastname: Malinin
authors.forename: David C
authors.initials: DC
authors.lastname: Sane
authors.forename: Bernd
authors.initials: B
authors.lastname: Jilma
authors.forename: Aviv
authors.initials: A
authors.lastname: Takserman
authors.forename: Dan
authors.initials: D
authors.lastname: Atar
authors.forename: Charles H
authors.initials: CH
authors.lastname: Hennekens
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000097:blood; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D000068342:Aspirin, Dipyridamole Drug Combination; D002545:Brain Ischemia / Q000150:complications; D023201:CD40 Ligand / Q000097:blood; D004176:Dipyridamole / Q000494:pharmacology / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood; D010979:Platelet Function Tests; D040201:Platelet Membrane Glycoprotein IIb / Q000097:blood; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D020521:Stroke / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D060185:Tetraspanin 24; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015703:Antigens, CD; D000068342:Aspirin, Dipyridamole Drug Combination; C554715:CD151 protein, human; D004338:Drug Combinations; D010975:Platelet Aggregation Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D040201:Platelet Membrane Glycoprotein IIb; D010980:Platelet Membrane Glycoproteins; D060185:Tetraspanin 24; D023201:CD40 Ligand; D004176:Dipyridamole; D001241:Aspirin