Aspirin, clopidogrel, and ticagrelor in acute coronary syndromes

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.