Given the increased hazard of recurrent cardiovascular events from premature discontinuation of P2Y12 inhibitors and the increased bleeding risk in patients undergoing procedures on therapy (eg, colonoscopy with biopsy, dental procedures), it is advisable to consult a cardiologist and preferably defer elective noncardiac procedures until the patient finishes the appropriate course of P2Y12 receptor inhibition therapy, especially in UA/NSTEMI patients who received 12 months of treatment with dual antiplatelet therapy after deployment of a drug-eluting stent (DES).15 3.2.3.1.3. Interindividual Variability in Responsiveness to Clopidogrel. Although clopidogrel in combination with as- pirin has been shown to reduce recurrent coronary events in the posthospitalized ACS population,13,16 the response to clopidogrel varies among patients, and diminished respon- siveness to clopidogrel has been observed.17,18 Clopidogrel is a prodrug and requires conversion to R130964, its active metabolite, through a 2-step process in the liver that involves several CYP450 isoenzymes19; of these, the CYP2C19 isoen- zyme is responsible for almost half of the first step forma- tion.20 At least 3 major genetic polymorphisms of the CYP2C19 isoenzyme are associated with loss of function: ants account for 85% and 99% of the loss-of-function alleles in Caucasians and Asians, respectively.20 There are racial and ethnic differences in the prevalence of these loss-of-function alleles among Caucasians, African Americans, Asians, and Latinos, but all of these groups have some expression of them. Data from a number of observational studies have dem- onstrated an association between an increased risk of adverse cardiovascular events and the presence of 1 of the nonfunc- tioning alleles17,18,20,21,23 27 and are well delineated in the ACCF/AHA Clopidogrel Clinical Alert.20 Prasugrel, the second FDA-approved P2Y12 receptor in- hibitor for use in ACS, is also a prodrug that requires conversion to its active metabolite. 