In TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel Thrombolysis In Myocardial Infarction)285 patients who were carriers of the reduced-function CYP2C19*2 allele had significantly lower levels of the active metabolite of clopi- dogrel, diminished platelet inhibition, and increased rates of major adverse cardiovascular events and stent thrombosis.285 The US Food and Drug Administration has changed clopido- grel s prescribing information to highlight the potential impact of CYP2C19 genotype on clopidogrel pharmacokinetics and Nevertheless, other studies have not con- firmed associations between CYP2C19 polymorphisms and adverse outcomes in clopidogrel-treated patients.290 Future studies are needed to further clarify the risk associated with these genetic polymorphisms and to develop effective thera- peutic strategies for carriers of allelic variants of responsible enzyme systems. Proton-pump inhibitors, most prominently omeprazole, can interfere with clopidogrel metabolism and result in diminished in vitro antiplatelet effect,291 but it does not appear that this pharmacokinetic effect translates into worse clinical outcomes.291,292 Prasugrel, an alternative thienopyridine, achieves greater inhibition of platelet aggregation than clopidogrel. In the of prasugrel versus clopidogrel in patients with ACS for whom an invasive strategy was planned, patientswithSTEMIwhowereassignedtoprasugrelhadalower 30-day rate of the composite primary outcome. This difference persisted to 15 months. In addition, the rate of stent thrombosis reported at 30 days was significantly lower with prasug- The loading dose of clopidogrel in TRITON-TIMI 38, which rarely was administered before coronary angiog- raphy and was limited to 300 mg, may have contributed to differences in efficacy and safety between treatment groups.262 The benefits of prasugrel relative to clopidogrel in STEMI must be weighed against the increase in the risk of bleeding associated with its use. 