The literature review was based on MEDLINE searches from 1966 through Feb. 2001. In addition, Current Contents and International Pharmaceutical Abstracts databases were searched from 1985 to February 2001. The search strategy, available online at www.aan.com, included controlled clinical trials and large-scale cohort studies.
The Committee also searched the Cochrane Database for pertinent randomized clinical trials and systematic reviews. Cochrane Reviews typically consist of formal meta-analyses of published and unpublished trials, not all of which are indexed in MEDLINE. These reviews were used to identify any relevant studies that may not have been found in the other searches. In addition, to help ensure that all pertinent studies were considered, a letter requesting relevant articles was sent to an international group of stroke experts who, in the opinion of the Joint Writing Committee, were considered authorities in the field of antithrombotic treatment of acute ischemic stroke.
Inclusion/Exclusion Criteria
The treatments selected by the Joint Writing Committee for review included unfractionated heparin, low molecular weight (LMW) heparin, heparinoids, aspirin, ticlopidine, clopidogrel, dipyridamole, hirudin, and glycoprotein IIb/IIIa antagonists. Reports of thrombolytics and fibrinogenolytics identified in the search were excluded because they are neither antiplatelet agents nor anticoagulants. Prostacyclin and pentoxyfylline were also excluded because they have major vascular effects other than antiplatelet actions. Case reports, studies of primary intracranial hemorrhages, studies that included only subjects with transient ischemic attack (TIA), and studies of dural sinus or cerebral vein thrombosis were also excluded.
To be considered for analysis, a study had to be a controlled clinical trial that tested an anticoagulant or antiplatelet agent in patients with an ischemic stroke. In addition, the drug must have been given within 48 hours of symptom onset. Clinical endpoints had to be clearly defined before the study started. Studies that included patients in whom treatment could be delayed after 48 hours were considered only if results were also separately on a well-defined subgroup of patients treated within 48 hours of symptom onset. A number of excellent and comprehensive papers on acute stroke management have been published recently, such as the recommendations from the European Stroke Initiative, but these reports did not meet criteria for inclusion since they were based upon reviews of other studies and expert opinion rather than primary source clinical trials.