Stroke is a leading cause of death and the primary cause of serious, long-term disability in the United States. Joint guidelines from the American Heart Association (AHA) and American
Stroke Association (ASA), as well as recent guidelines from the Eighth American College of Chest Physicians (ACCP) Conference on Antithrombotic and Antiplatelet
Therapy, recommend
aspirin,
clopidogrel, or extended-release
dipyridamole plus
aspirin as acceptable first-line options for
secondary prevention of ischemic events in patients with a history of
ischemic stroke or
transient ischemic attack (TIA). The ACCP strongly recommends the combination of extended-release
dipyridamole plus
aspirin over
aspirin monotherapy (highest level of evidence) and suggests
clopidogrel monotherapy over
aspirin monotherapy (lower level of evidence). The AHA-ASA guidelines suggest that either extended-release
dipyridamole plus
aspirin or
clopidogrel monotherapy should be used over
aspirin monotherapy. Both guidelines recommend avoiding the combination of
clopidogrel and
aspirin for most patients with previous
stroke or TIA. Results from recent trials evaluating combination antiplatelet
therapy have been published that enhance the AHA-ASA recommendations and provide the foundation for the updated ACCP guideline. To identify pertinent combination antiplatelet trials, a MEDLINE search of the literature from 1967-2007 was performed. Two trials were identified--the European-Australasian
Stroke Prevention in Reversible
Ischemia Trial (
ESPRIT) and
Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA). The
ESPRIT compared
aspirin monotherapy with the combination of
aspirin plus extended-release
dipyridamole for prevention of secondary ischemic events in patients with a history of TIA or minor
stroke. The CHARISMA trial compared
aspirin plus
clopidogrel with
aspirin alone in a population at high risk for atherothrombotic events using the composite outcome of
myocardial infarction,
stroke, and death from cardiovascular causes. Data from
ESPRIT add to evidence that the combination of
aspirin plus extended-release
dipyridamole is superior to
aspirin alone. The findings of the CHARISMA trial reinforce recommendations from both AHA-ASA and ACCP that the combination of
aspirin and
clopidogrel be reserved for special populations requiring this antiplatelet combination (e.g., those who have had coronary artery stenting).