Pretreatment with P2Y12 inhibitors in non-ST-Segment-elevation acute coronary syndrome: an outdated and harmful strategy.

Abstract

Coronary plaque rupture that occurs during the acute coronary syndrome (ACS) results in the deposition and activation of platelets and the formation of thrombi. The platelet mediators thromboxane A2 and ADP have been demonstrated to play a dominant role in the initiation and propagation of coronary thrombosis, representing key therapeutic targets in the management of ACS. Early inhibition of these biomarkers with oral administration of aspirin and a P2Y12 receptor inhibitor together with anticoagulation has been recommended to avoid complete thrombotic occlusion, which may occur during the initial platelet response to vascular injury when the diagnosis of non–ST-segment–elevation ACS (NSTE-ACS) is made or after percutaneous coronary intervention (PCI). An early invasive strategy of cardiac catheterization and revascularization is recommended in patients in whom the thrombotic burden is the highest. A routine invasive versus selective invasive strategy was shown to reduce the rates of death and myocardial infarction, with the most pronounced difference in these high-risk patients.1 In particular, an early catheterization followed by coronary intervention on the first day of hospitalization was shown to be safe and superior in terms of lower risk of recurrent ACS (−41%) and shorter hospital stay (−28%).2 The strategy of “sooner is better” for catheterization suggests also having the same strategy for antiplatelet strategy, which has remained unproven. Guidelines have recommended early initiation of dual antiplatelet therapy, a combination of aspirin and clopidogrel, as soon as possible when the diagnosis of high-risk NSTE-ACS is made, although the timing of loading remained unclear.3,4 This concept of treatment of NSTE-ACS at the time of presentation or admission is known as pretreatment, a treatment given when the diagnosis is suspected and always before the coronary status is known to confirm the diagnosis of coronary artery disease (CAD) and to make the …