Patients experiencing
stroke or
transient ischemic attack (TIA) are at high risk for recurrent (secondary)
strokes, which comprise 29% of all
strokes in the United States. Current recommendations for prevention of secondary
stroke from the American College of Chest Physicians (ACCP) call for the broad use of platelet antiaggregation (
antiplatelet) agents for patients with a history of noncardioembolic
stroke or TIA. Five agents--
aspirin,
ticlopidine,
clopidogrel, extended-release
dipyridamole (ER-DP), and
triflusal--have demonstrated efficacy in large-scale clinical studies in the prevention of recurrent vascular events and/or
stroke in patients with a history of
stroke. The results of the following studies are reviewed and compared: the Swedish
Aspirin Low-Dose Trial (
SALT), the United Kingdom Transient Ischaemic Attack (UK-TIA)
Aspirin Trial, Dutch
Transient Ischemic Attack (Dutch TIA) study (
aspirin), the Canadian American
Ticlopidine Study (CATS), the
Ticlopidine Aspirin Stroke Study (TASS), the African American Antiplatelet
Stroke Prevention Study (AAASPS) (
ticlopidine), the
Clopidogrel versus
Aspirin in Patients at Risk of Recurrent Ischemic Events (CAPRIE) trial, the Management of
Atherothrombosis With
Clopidogrel in High-Risk Patients study (MATCH) (
clopidogrel), the second European
Stroke Prevention Study (ESPS2) (
aspirin plus ER-DP), and the
Triflusal versus
Aspirin in
Cerebral Infarction Prevention (TACIP) study. In comparative monotherapy studies of patients with previous
stroke,
ticlopidine demonstrates statistically significant improved efficacy over
aspirin, and
clopidogrel demonstrates nonsignificant slight improvement over
aspirin for the prevention of ischemic cardiac and cerebrovascular events; however, the adverse event profile of
ticlopidine (including
rash,
diarrhea, and
neutropenia) will probably limit its long-term use. Among combination approaches, only
aspirin plus ER-DP has demonstrated statistically significant, clinically meaningful additive benefit over monotherapy with each agent.
Clopidogrel plus
aspirin did not significantly improve preventive efficacy and increased the risk of serious side effects, including life-threatening
bleeding episodes. The 15,500-patient PRoFESS (the Prevention Regimen for Effectively Avoiding Second
Strokes) study, with results expected in 2008, will directly compare
aspirin plus ER-DP with
clopidogrel monotherapy for the prevention of recurrent
stroke and should provide statistically robust estimates of comparative efficacy for the development of improved recommendations.