Jneid et al.1 recommended the use of prasugrel as an alternative to clopidogrel in ACS patients undergoing percutaneous coronary intervention (PCI), cautioned against its use in those with a history of stroke or

transient ischemic attack because of observed net clinical harm (as shown previously3), and recommended its empiric discontinuation at least 7 days before planned CABG (Table 1). It is important to note that TRITON-TIMI 38 enrolled Inhibitors,research,lifescience,medical ACS patients scheduled to undergo PCI, of whom 74% had non-ST-elevation ACS, and did not enroll medically-treated ACS patients. In addition, prasugrel was compared with a 300-mg loading dose of clopidogrel followed by 75-mg daily maintenance, which was the antiplatelet regimen used in the CURE study.4-6 This regimen, Inhibitors,research,lifescience,medical which achieves a slower platelet inhibition compared with a 600-mg loading dose, was recently shown to be inferior to the double-dosing

regimen examined in the CURRENT-OASIS 7 trial.7 Post hoc analyses from TRITON-TIMI 382 identified two additional subgroups in whom prasugrel had no net Inhibitors,research,lifescience,medical favorable clinical benefit: patients ≥75 years of age and those <60 kg of weight. Table 1 Summary of important recommendations in the 2012 ACCF/AHA focused updates of the UA/NSTEMI guidelines. Gamma-secretase inhibitor in clinical trial ticagrelor Ticagrelor, a nonthienopyridine P2Y12 inhibitor therapy, is a reversible agent that was shown to be superior to clopidogrel in reducing ischemic events in the Inhibitors,research,lifescience,medical PLATO trial.8 PLATO was a landmark trial that included 18,624 medically and invasively treated ACS patients, roughly 60% of whom had non-ST-elevation ACS.8 Using a double-blind, double-dummy design, PLATO compared ticagrelor (180-mg loading dose followed by 90 mg twice daily) with clopidogrel (300- to 600-mg loading dose followed by 75 mg daily). The primary efficacy endpoint was the time to first occurrence of the composite of vascular death, MI, or stroke. At 12 months, ticagrelor was associated Inhibitors,research,lifescience,medical with a 16% relative reduction in the primary composite outcome compared with clopidogrel, which was driven by lower rates of MI and

vascular death. The benefits of ticagrelor appeared consistent across most Nature Cell Biology subgroups. Importantly, ticagrelor was associated with a remarkable 1.4% absolute risk reduction in all-cause mortality (4.5% versus 5.9%; HR: 0.78; 95% CI: 0.69–0.89), and with significantly lower rates of definite stent thrombosis. There were no significant differences between the ticagrelor and clopidogrel groups in the rates of PLATO major bleeding (the primary safety endpoint), TIMI major bleeding, or fatal bleeding. However, ticagrelor was associated with a higher rate of non-CABG-related major bleeding and caused a higher incidence of dyspnea (not necessitating drug discontinuation except in a few cases) and a higher rate of ventricular pauses ≥3 seconds in the first week.