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Platelet-Active Drugs : The Relationships Among Dose, Effectiveness, and Side Effects

Carlo Patrono, MD, Chair; Barry Coller, MD; James E. Dalen, MD, FCCP; Garret A. FitzGerald, MD; Valentin Fuster, MD; Michael Gent, DSc; Jack Hirsh, MD, FCCP; Gerald Roth, MD
Author and Funding Information

Affiliations: *Dr. Patrono was supported in part by grant 97.04882.ST74 from the Consiglio Nazionale delle Ricerche, Progetto Strategico “Infarto Miocardico” and by grant 9706570507 005 from the Italian Ministry of University and Research. ,  Dr. Coller is a coinventor of abciximab, an inventor of the technology underlying the rapid platelet function assay being developed by Accumetrics, San Diego, CA, a member of the scientific advisory board of Accumetrics, and a stockholder in Accumetrics. Supported in part by grants 19278 and 54469 from the National Heart, Lung, and Blood Institute. Dr. Coller did not participate in developing any specific recommendations concerning the use of GPIIb/IIIa antagonists or the value of monitoring GPIIb/IIIa antagonist therapy. ,  Dr. FitzGerald is the Robinette Foundation Professor of Cardiovascular Medicine. His work is supported by grants HL 62250, HL 61364, HL 54500, and RR 00040.

Correspondence to: Carlo Patrono, MD, Department of Medicine and Aging, Università degli Studi G D’Annunzio, Via Dei Vestini 31, 66013 Chieti, Italy; e-mail: cpatrono@unich.it



Chest. 2001;119(1_suppl):39S-63S. doi:10.1378/chest.119.1_suppl.39S
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Since our last report on antithrombotic therapy in 1998,1 new information has been published on the role of aspirin and other platelet-active drugs in the treatment and prevention of atherothrombosis. These new data can be summarized as follows: (1) a large randomized study, the Acetylsalicylic Acid and Carotid Endarterectomy (ACE) trial,2 has directly compared low-dose and high-dose aspirin for the prevention of ischemic stroke in patients undergoing carotid endarterectomy; (2) the role of aspirin in prophylaxis of venous thromboembolism (VTE) has to be reassessed in the light of the Pulmonary Embolism Prevention (PEP) trial3; (3) three nonrandomized studies with historical control subjects46 and one randomized trial7 have compared the safety of clopidogrel plus aspirin vs ticlopidine plus aspirin in patients undergoing intracoronary stent implantation; (4) the results of clinical and angiographic follow-up of the patients in the Evaluation of Platelet IIb/IIIa Inhibitors for Stenting (EPISTENT) trial at 6 months8 and 1 year9 provide evidence that stent implantation and platelet glycoprotein (GP) IIb/IIIa blockade by abciximab improve the efficacy and safety of percutaneous coronary revascularization; and (5) preliminary reports from three large trials of long-term GPIIb/IIIa blockade (Orbofiban in Patients with Unstable Coronary Syndromes [OPUS]; Evaluation of Xemilofiban in Controlling Thrombotic Events [EXCITE]10; and sibrafiban vs aspirin to yield maximum protection from ischemic heart events post-acute coronary syndromes [SYMPHONY] (sibrafiban)11) in approximately 27,000 patients taking oral drugs for 3 months to 1 year, are largely disappointing in terms of efficacy and/or safety.12

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