[Antiplatelet therapy in acute coronary syndromes: state of the art and new perspectives]

Abstract

Antiplatelet therapy plays a pivotal role in the treatment of patients with acute coronary syndromes (ACS), inducing a significant reduction of ischemic events. Aspirin treatment is associated with a substantial 50% reduction of death or myocardial infarction in patients with ACS, but it is usually combined with other antiplatelet agents in order to achieve a more profound inhibition of platelet aggregation. Ticlopidine was initially used in association with aspirin in patients treated with percutaneous coronary interventions (PCI), demonstrating a dramatic reduction of the risk of stent thrombosis. Later on it has been replaced by clopidogrel, which now represents in combination with aspirin the standard treatment of patients with ACS treated either medically or invasively, with a 20% risk reduction in comparison with aspirin alone. The limitation of clopidogrel resistance, documented in about 30% of patients because of genetic factors, clinical factors, and pharmacokinetic factors (i.e., poor absorption and drug-drug interactions), has promoted the development of third generation thienopiridines. Prasugrel, which is a more potent and faster inhibitor of platelet aggregation, in comparison with clopidogrel is associated with a further 20% reduction of ischemic events with an increase of major bleedings in patients with ACS undergoing PCI. It is therefore recommended for patients with ACS at high ischemic risk and at non-high hemorrhagic risk. Ticagrelor, a reversible antagonist of P2Y12 platelet receptor, in comparison with clopidogrel is associated with a 16% reduction of ischemic events, including a significant reduction of death from vascular causes, without increasing the rate of overall major bleeding. Intravenous cangrelor, which has been compared with clopidogrel in patients with ACS undergoing PCI, yielded negative results. The use of glycoproteins IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban) is no longer recommended as upstream therapy in patients with ACS undergoing PCI, but only in the periprocedural phase. New selective antagonists of thrombin receptor 1 (PAR-1), on top of the standard dual antiplatelet therapy, are now under investigation in patients with ACS and in the secondary prevention. In conclusion, an accurate evaluation is warranted of the balance between ischemic and hemorrhagic risk when deciding the choice of antiplatelet treatment in the individual patient. The hope for the future is the development of new selective platelet inhibitors with higher antischemic efficacy and better hemorrhagic profile.