Atherothrombosis is the major underlying cause of
acute coronary syndromes,
ischemic stroke, and
peripheral artery disease, and thus is the leading cause of death and disability in Western countries.
Platelet inhibitors play a major role in preventing these ischemic complications. There is strong evidence from the Antiplatelet Trialists' Collaboration meta-analysis that
aspirin reduces the combined risk of
stroke,
myocardial infarction (MI), or vascular death in atherosclerotic patients. The
Ticlopidine Aspirin Stroke Study (TASS) compared
aspirin and
ticlopidine in the
secondary prevention of high-risk patients after
ischemic stroke and demonstrated a significant advantage for
ticlopidine over
aspirin. In
peripheral arterial disease, the Swedish
Ticlopidine Multicentre Study (STIMS) showed that
ticlopidine was very effective against placebo. Intravenous
antiplatelet agents, such as
abciximab,
tirofiban, and eptifibitide were also proven effective in
acute coronary syndromes and
unstable angina. In the
Clopidogrel versus
Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) trial,
clopidogrel was compared with
aspirin in patients with symptomatic
atherothrombosis regardless of the initial localization of the ischemic event (coronary, cerebral, or peripheral). The efficacy of
clopidogrel based on the first occurrence of
ischemic stroke, MI, or vascular death showed a relative risk reduction of 8.7% over and above the 25% reduction currently accepted with
aspirin (p < 0.05). The greatest benefit of
clopidogrel was in the reduction of fatal and nonfatal MI in the most severe groups of patients, providing
a 19% relative risk reduction (p = 0.008). The recent disappointing results obtained with oral
glycoprotein IIb/IIIa receptor blocking agents may emphasize the need for other antiplatelet combination
therapy, such as
aspirin-
clopidogrel, in
coronary disease,
stents,
stroke, and possibly
atherothrombosis in high-risk patients.