Rapid P2Y 12 Inhibition

Acute coronary syndrome (ACS) is still a serious condition associated with decreased quality of life, increased healthcare expenditures, and premature death. The prevalence of ACS is expected to increase with aging of the population and with the epidemics of obesity and diabetes. The short- and long-term mortality after an ACS has been dramatically reduced by the development of revascularization techniques and new antithrombotic agents. The past decade has seen many trials evaluating new oral and parenteral antiplatelet agents with greater potency than aspirin and clopidogrel. Several antiplatelet agents have been developed, with the ultimate goal to obtain optimal antiplatelet therapy for both the acute and the chronic phases of disease.Articles see p 336, 347Ideally, efficiency requires several pharmacodynamic proprieties, such as a fast onset of action (immediate onset for emergency situations), a strong degree of platelet inhibition (at least stronger than the standard of care [aspirin and clopidogrel]), a narrow interindividual variability with no impact of genetic variants and no drug-to-drug interaction, and an easy administration (an oral drug for maintenance therapy and an intravenous formulation for rapid loading). Of course, this drug should also lead to a convincing reduction of recurrent ischemic events in an adequately powered phase 3 trial.With regard to safety, the illusion of having the same dose of a single antiplatelet drug to treat all clinical situations has passed. The degree of platelet activation and aggregation is different across clinical situations (eg, acute ST-segment–elevation myocardial infarction [STEMI] versus secondary prevention) and varies over time in the same patient. Recent large phase 3 trials have confirmed the importance of dosing and the target population treated with the new agents.1–4 From a safety standpoint, an ideal antiplatelet agent would also have an intravenous and oral formulation, with different doses tested in …