3, 15 Although the exact mechanism is unknown, several theories include loss of estrogen, catecholamine excess, neurohumoral stimulation, coronary artery spasm, and LVOT obstruction.3-5, 15, 17 Conflict of Interest Disclosure: All authors have completed and submitted the Methodist 5-FU in vivo DeBakey Cardiovascular Journal Conflict of Interest Statement and none were reported. Funding/Support: The authors have no funding disclosures. Contributor Information Pradnya Velankar, Methodist DeBakey Heart & Vascular Center, Houston, Texas. John Buergler, Methodist

DeBakey Heart & Vascular Center, Houston, Texas.
Introduction The American College of Cardiology Foundation (ACCF) and the American Heart Association Inhibitors,research,lifescience,medical (AHA) recently published the 2012 Inhibitors,research,lifescience,medical ACCF/AHA Focused Update of the Guidelines for the Management of Patients with Unstable Angina and Non-ST-Elevation Myocardial Infarction (Updating the 2007 Guideline and Replacing the 2011 Update).1 These guidelines were developed in collaboration with multiple societies and represent an important landmark in the management of patients with unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI). This paper provides a critical overview of some of the clinically relevant novel and modified recommendations

proposed by the updated guideline. Oral Antiplatelet Therapies Prasugrel Prasugrel was incorporated Inhibitors,research,lifescience,medical into the 2012 focused update1 following the results of the TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infarction Inhibitors,research,lifescience,medical (TRITON-TIMI

38)2 and its subsequent FDA approval in July 2009. Like clopidogrel, prasugrel is an irreversible inhibitor of the P2Y12 receptor; however, it has quicker onset of action (within 30 minutes), achieves greater inhibition of adenosine diphosphate-induced platelet Inhibitors,research,lifescience,medical aggregation, and is associated with lesser variability related to drug metabolism or genetic pleomorphism. TRITON-TIMI 382 was a pivotal randomized controlled trial that evaluated the efficacy of prasugrel versus clopidogrel in 13,608 moderate- to high-risk patients with acute coronary syndrome (ACS). The trial demonstrated a 19% significant reduction in the composite of cardiovascular death, MI, or stroke with prasugrel (60-mg most loading followed by 10-mg daily doses) compared with clopidogrel at a mean of 15-months follow-up. This salubrious outcome was driven by a reduction in nonfatal MI, was observed as early as 3 days post-randomization, and was accompanied by a reduction in urgent target vessel revascularization (TVR) and stent thrombosis (ST) in the prasugrel group.2 The benefits of prasugrel versus clopidogrel were tempered by an increase in non-CABG TIMI major bleeding events (the key safety endpoint) (2.4% vs. 1.8%; P = 0.03), including more life-threatening and fatal bleeding events.