Do not use prasugrel in patients with active pathological bleeding or a history of TIA or stroke. In patients age 75 y, prasugrel is generally not recommended because of the increased risk of fatal and intracranial bleeding and uncertain benefit, except in high-risk situations (patients with diabetes or a history of prior myocardial infarction), for which its effect appears to be greater and its use may be considered. Do not start prasugrel in patients likely to undergo urgent CABG. When possible, discontinue prasugrel at least 7 d before any surgery. Additional risk factors for bleeding include body weight 60 kg, propensity to bleed, and concomitant use of medications that increase the risk of bleeding (eg, warfarin, heparin, fibrinolytic therapy, or long-term use of nonsteroidal anti-inflammatory drugs). ACT indicates activated clotting time; ASA, aspirin; BMS, bare-metal stent; CABG, coronary artery bypass graft; DES, drug-eluting stent; GP, glycoprotein; FDA, Food and Drug Administration; ICH, intracranial hemorrhage; IV, intravenous; LD, loading dose; LOE, level of evidence; MACE, major adverse cardiac events; MD, maintenance dose; PCI, percutaneous coronary intervention; PLATO, PLATelet inhibition and patient Outcomes trial; PPI, proton pump inhibitor; STEMI, ST-elevation myocardial infarction; TIA, transient ischemic attack; UA/NSTEMI, unstable angina/non ST-elevation myocardial infarction; and UFH, unfractionated heparin. Modified from Wright et al.6 Jneid et al 2012 UA/NSTEMI Focused Update 907 Appendix 4. Comparisons Among Orally Effective P2Y12 Inhibitors Clopidogrel Prasugrel Ticagrelor Pharmacology Prodrug requires conversion to active metabolite that irreversibly blocks P2Y12 receptor Prodrug requires conversion to active metabolite that irreversibly blocks P2Y12 receptor. 