Balancing Benefit and Bleeding Risk of Antithrombotic Agents in the Individual Patient With an Acute Coronary Syndrome

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In most countries, the antithrombotic armamentarium for treating acute coronary syndrome (ACS) patients currently consists of aspirin, clopidogrel, heparin, enoxaparin, bivalirudin, and fondaparinux. A large number of new antithrombotic agents for treating ACS patients are about to enter the market or are under development: new P2Y12 inhibitors (prasugrel, ticagrelor, cangrelor), thrombin receptor (proteinase-activator receptor-1) antagonists (SCH 530348, E555), direct antithrombin (dabigatran), and anti-Xa agents (otamixaban, rivaroxaban, apixaban).1 For all these new agents, there is evidence of enhanced or additional antithrombotic efficacy compared with standard antithrombotic regimens. A remaining clinical challenge of major importance is the price to be paid in terms of extra bleeding complications. For example, although there is very convincing evidence that prasugrel reduces the risk of stent thrombosis compared with clopidogrel, the practicing physician might be hesitant to put a particular ACS patient undergoing percutaneous coronary intervention on prasugrel because of the increased risk of a major or even fatal bleeding complication as demonstrated in the total population treated with prasugrel in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel (TRITON).2 What the practicing physician would like to know is, In which patients does the reduced risk of stent thrombosis with prasugrel by far outweigh the risk of a severe and possibly fatal bleeding? Article see p 43 Risk factors for bleeding complications have been identified in several previous studies: eg, age,3 female gender,3,4 renal impairment,3,4 and previous bleeding.3 Some of these risk factors such as age, renal failure, and hypertension have been shown in large registries to also be risk factors for recurrent ischemic events and death (summarized, for instance, by Gale et al5 and Diez and Cohen6). Thus, identifying these risk factors in a particular patient is not very helpful. In …