Dual antiplatelet
therapy is the cornerstone in the management of patients with
acute coronary syndromes (ACS).
Ticagrelor, an oral, direct, reversibly binding, P2Y₁₂ receptor antagonist, is approved for the prevention of atherothrombotic events in adult patients with ACS. In the PLATelet inhibition and patient Outcomes (PLATO) trial,
ticagrelor was associated with significant reductions in cardiovascular events, cardiovascular mortality, and all-cause mortality compared with
clopidogrel. A subanalysis of PLATO trial data identified a geographic region interaction (p = 0.045), indicating reduced efficacy of
ticagrelor versus
clopidogrel in North American patients. This effect could be due to chance, but may be explained by an interaction of
ticagrelor with high
aspirin doses, which are commonly used in the United States. In patients taking low-dose maintenance
aspirin,
ticagrelor was more effective than
clopidogrel in decreasing cardiovascular events regardless of the geographic region. A proposed hypothetical mechanism for the interaction between
ticagrelor and higher
aspirin dose is linked to the level of P2Y₁₂ inhibition and the potential prothrombotic effects of high-dose
aspirin through the suppression of
prostacyclin. A review of data regarding
aspirin use for
secondary prevention of events in ACS demonstrated that low
aspirin doses (75 to 160 mg/day) are consistently favored for short- and long-term use because of the lack of a dose-response relationship between increasing
aspirin dose and improved efficacy, and a higher incidence of gastrointestinal
bleeding with increasing
aspirin dose. The use of low
aspirin doses reflects good clinical practice and is encouraged in current guidelines.