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

Abstract

Since our last report on antithrombotic therapy in 1995, 1 Hirsh J Dalen JE Fuster V et al. Aspirin and other platelet-active drugs: the relationship among dose, effectiveness and side effects. Chest. 1995; 108: 247S-257S Abstract Full Text Full Text PDF PubMed Google Scholar 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) two large randomized studies have tested the efficacy and safety of aspirin in patients with acute ischemic stroke; 2 International Stroke Trial Collaborative GroupThe International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19,435 patients with acute ischemic stroke. Lancet. 1997; 349: 1569-1581 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar ,3 CAST (Chinese Acute Stroke Trial) Collaborative GroupCAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischemic stroke. Lancet. 1997; 349: 1641-1649 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar (2) two recent studies have shown that low-dose aspirin therapy is effective and safe in the primary prevention of ischemic heart disease in men at high risk 4 The Medical Research Council's General Practice Research FrameworkThrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischemic heart disease in men at increased risk. Lancet. 1998; 351: 233-241 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar as well as in men and women with hypertension; 4a Hansson L Zanchetti A Carruthers SG et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet. 1998; 351: 1755-1762 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar (3) the clinical efficacy of dipyridamole has to be reassessed in the light of the European Stroke Prevention Study-2 (ESPS-2); 5 Diener HC Cunha L Forbes C et al. European Stroke Prevention Study: II. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996; 143: 1-13 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar (4) a novel thienopyridine derivative, clopidogrel, has been shown to be at least as effective as aspirin in one very large phase III trial 6 CAPRIE Steering CommitteeA randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischemic events (CAPRIE). Lancet. 1996; 348: 1329-1339 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar and may be a safer alternative to aspirin than ticlopidine; (5) besides abciximab, now on the market in many countries, several platelet glycoprotein (GP) IIb/IIIa (integrin αIlbβ3) antagonists are in various stages of clinical development and have shown improved efficacy over conventional antithrombotic treatment in high-risk acute coronary settings; 7 Anderson KM Weisman HF Coller BS. Platelet glycoprotein IIb/IIIa receptor inhibitors. in: Hennekens CH Buring JE Manson JE Clinical trials in cardiovascular disease. WB Saunders, Philadelphia1999 Google Scholar and (6) the additive effect of ticlopidine and aspirin in the prevention of coronary stent thrombosis has been demonstrated, 8 STARSN Engl J Med. 1998; (in press) Google Scholar while controversial results have been reported for the combination of low-dose aspirin with low-intensity oral anticoagulation with warfarin. 4 The Medical Research Council's General Practice Research FrameworkThrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischemic heart disease in men at increased risk. Lancet. 1998; 351: 233-241 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar ,9 Coumadin Aspirin Reinfarction Study (CARS) InvestigatorsRandomised double-blind trial of fixed low-dose warfarin with aspirin after myocardial infarction. Lancet. 1997; 350: 389-396 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar