Platelet activation and aggregation play a pivotal role in thrombotic complications occurring during percutaneous coronary intervention (PCI), and peri-PCI anti-platelet therapy represents a standard of care. High platelet reactivity prior to PCI has been correlated with an increased incidence of peri-procedural myonecrosis. Pre-PCI platelet reactivity predicts post-PCI platelet reactivity and has a prognostic impact on subsequent ischaemic and bleeding events, so as the platelet inhibition measured post-PCI. Many anti-platelet treatment strategies, including aspirin, glycoprotein IIb/IIIa inhibitors, P2Y receptor blockers and vorapaxar, are being used in the routine clinical practice to modify platelet reactivity at each stage, e.g. pre-, during and post-PCI. Anti-platelet strategies with a 'stronger and faster' pharmacodynamic effect than clopidogrel have been mostly adopted in patients with acute coronary syndromes. However, several issues regarding the anti-platelet treatment such as benefits/risks of anti-platelet therapy pre-treatment and duration, and definite association between speed and potency of various anti-platelet agents and clinical outcomes remain controversial. We believe that a better understanding of peri-PCI platelet reactivity and its relations to outcomes may lead to the development of more effective and safe treatment strategies.
Triple antithrombotic therapy (TAT), consisting of aspirin, a P2Y receptor antagonist and oral anticoagulant (OAC) medication has been considered as an 'unavoidable' strategy for a 1-12 months for atrial fibrillation (AF) patients post acute coronary syndrome or percutaneous coronary angioplasty with stenting. However, TAT has rather poorly been adopted in real life practice, mainly because of an accompanying increased bleeding potential and lack of definitive results of randomized clinical trials. Several registries, meta-analyses and small randomized trials have so far provided the base of guidelines recommendations. Furthermore, in the recently published Open-Label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects with Atrial Fibrillation who Undergo Percutaneous Coronary Intervention (PIONEER AF-PCI) trial involving 2124 patients, the primary safety endpoint of clinically significant bleeding was significantly reduced in the rivaroxaban low dose (15 mg daily) plus single P2Y receptor antagonist arm compared to TAT, with no difference in the secondary efficacy endpoint. Despite several limitations of the PIONEER AF-PCI trial, it appears that among patients who omit aspirin, there may be equivalent ischemic protection with dual therapy and no disadvantage for additional risk of thrombotic events.
In patients with an acute coronary syndrome undergoing percutaneous coronary intervention, novel P2Y 12 receptor inhibitors, prasugrel and ticagrelor, are proposed as "first-line" antiplatelet agents in the absence of contraindications and up to a year from the index event. However, de-escalation of treatment to clopidogrel occurs with a variable frequency in real-life practice, most commonly due to an increased bleeding potential, more frequent side effects, and a higher cost for the novel agents. Pharmacodynamic studies provide most of the data on guidance for de-escalation. Despite positive messages from recent trials and registries, lack of definitive efficacy or safety results of such a strategy remains an obstacle to suggest de-escalation in a routine basis. Carefully designed studies are likely to improve our understanding of the impact of de-escalation and help to better define its position in current pharmacotherapy.
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