title: Antiplatelet therapy in ischemic stroke: variability in clinical trials and its impact on choosing the appropriate therapy.
abstract: Antiplatelet therapy is an integral component of effective secondary prevention after non-cardioembolic ischemic stroke. Numerous clinical trials have tested the efficacy and safety of different antiplatelet regimens, including aspirin monotherapy, clopidogrel monotherapy, the combination of aspirin plus clopidogrel, and the combination of aspirin plus dipyridamole, in patients with a history of arterial ischemic stroke and transient ischemic attack (TIA). Although competing, head-to-head comparisons between aspirin plus dipyridamole and clopidogrel were not previously available, various professional societies have outlined evidence-based recommendations for antiplatelet therapy in patients with ischemic stroke or TIA. Based on these guidelines, many experts in the field implicitly assumed that aspirin plus extended-release dipyridamole was the most effective antiplatelet treatment for stroke patients. However, these assumptions were called into question upon publication of the results from the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. The results of PRoFESS thus highlight the pitfalls of making conclusions of relative therapy efficacy in the absence of head-to-head comparisons. This article presents an overview of the factors that differ between clinical trials and "real-world" patient populations, as well as factors that differ among clinical trials themselves. The article also addresses the potential impact these differences may have on clinical trial results and subsequent clinical decision making.
authors.affiliation: Department of Neurology, Stritch School of Medicine, Loyola University Chicago, 2160 S. 1st Avenue, Bldg. 105, Room 2700, Maywood, IL 60153, United States. jbiller@lumc.edu
authors.forename: José
authors.initials: J
authors.lastname: Biller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D050197:Atherosclerosis / Q000150:complications; D002545:Brain Ischemia / Q000188:drug therapy* / Q000453:epidemiology; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D000077144:Clopidogrel; D015986:Confounding Factors, Epidemiologic; D003657:Decision Making; D004176:Dipyridamole / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D019317:Evidence-Based Medicine; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D018579:Patient Selection; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012107:Research Design; D055502:Secondary Prevention; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin