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After a month of treatment, platelet responsiveness to clopidogrel was superior in the group given pantoprazole with fewer nonresponders (44% vs. 23%; p = 0.04), suggesting the preferential use of pantoprazole in the setting of clopidogrel therapy. The complexity of clopidogrel's metabolism was further emphasized in an analysis of the CLARITY�CTIMI 28 (Clopidogrel as Adjunctive Reperfusion Therapy�CThrombolysis In Myocardial Infarction 28) trial (37). Building on an initial report in the Journal in 2008 from Bliden et al. ( 38), which showed an association of cigarette smoking, a known inducer of the cytochrome p450 system, with enhanced response to clopidogrel, the authors examined the interaction of clopidogrel and smoking in 3,429 STEMI patients and its impact on clinical outcomes. Rapamycin concentration They found that smokers (at least 10 cigarettes a day) had a particularly enhanced benefit from clopidogrel (adjusted OR for a closed infarct-related artery or death/MI before angiography of 0.49 compared with 0.72). The Flavoprotein findings should, of course, not be seen as an endorsement of smoking but rather as further highlighting the importance of clopidogrel activation by the cytochrome system. Clopidogrel initiation prior to early invasive management is recommended by the ACC/AHA guidelines for ACS patients, but is often withheld due to concerns that bleeding may occur if the patient is referred for coronary artery bypass graft (CABG) surgery. In an analysis from the ACUITY trial, Ebrahimi et al. (39) examined the outcomes in 1,539 patients ABT263 who underwent CABG. They found a reduction in ischemic events (12.7% vs. 17.3%, p = 0.01), without an increase in bleeding. Importantly, in the trial, a 5-day washout period was recommended, and there was an increased rate of transfusion in those that had early CABG (