International Expert Consensus on Switching Platelet P2Y ₁₂ Receptor–Inhibiting Therapies

Abstract

Dual antiplatelet therapy with aspirin and a P2Y 12 inhibitor is the treatment of choice for the prevention of atherothrombotic events in patients with acute coronary syndromes and for those undergoing percutaneous coronary interventions. The availability of different oral P2Y 12 inhibitors (clopidogrel, prasugrel, ticagrelor) has enabled physicians to contemplate switching among therapies because of specific clinical scenarios. The recent introduction of an intravenous P2Y 12 inhibitor (cangrelor) further adds to the multitude of modalities and settings in which switching therapies may occur. In clinical practice, it is not uncommon to switch P2Y 12 inhibitor, and switching may be attributed to a variety of factors. However, concerns about the safety of switching between these agents have emerged. Practice guidelines have not fully elaborated on how to switch therapies, leaving clinicians with limited guidance on when and how to switch therapies when needed. This prompted the development of this expert consensus document by key leaders from North America and Europe with expertise in basic, translational, and clinical sciences in the field of antiplatelet therapy. This expert consensus provides an overview of the pharmacology of P2Y 12 inhibitors, different modalities and definitions of switching, and available literature and recommendations for switching between P2Y 12 inhibitors. Dual antiplatelet therapy with aspirin and a platelet P2Y 12 receptor antagonist (P2Y 12 inhibitor) is the treatment of choice for the prevention of atherothrombotic events in patients with acute coronary syndromes (ACS) and for those undergoing percutaneous coronary intervention (PCI).1,2 Clopidogrel, prasugrel, and ticagrelor are the most commonly used oral platelet P2Y 12 inhibitors; the use of ticlopidine, the first available P2Y 12 inhibitor, has been largely abandoned. 3Clopidogrel is the only oral P2Y 12 inhibitor indicated for the treatment of patients with stable coronary artery disease.1,2 Although all 3 agents have an indication for use in ACS, current guidelines support the preferential use of prasugrel and ticagrelor over clopidogrel because of their superior net clinical benefits.1,2,4-6 Nevertheless, clopidogrel remains widely prescribed. 7,8 The availability of different oral P2Y 12 inhibitors has enabled physicians to contemplate switching among therapies because of specific clinical scenarios. 9 The recent introduction of an intravenous P2Y 12 inhibitor (ie, cangrelor) further adds to the multitude of modalities and settings in which switching therapies may occur. 6 A variety of factors may contribute to the decision to switch, including the clinical setting, patient characteristics, concomitant therapies, costs, social issues, development of side effects, medication adherence, and patient/physician preference. Therefore, it is not uncommon to change P2Y 12 inhibitor. However, concerns about the safety of switching between these agents have emerged. At present, data from large-scale clinical studie...

Switching from ticagrelor to clopidogrel in patients with ST‐segment elevation myocardial infarction undergoing successful percutaneous coronary intervention in real‐world China: Occurrences, reasons, and long‐term clinical outcomes

“…Our result supported the SCOPE registry, which has shown that de‐escalation increased the rate of adverse cardiovascular events in the first month after hospital discharge . Some studies assessing the pharmacodynamic effects associated with de‐escalation to clopidogrel therapy have shown a reduction in platelet‐inhibition and an increase in the rate of high on‐treatment platelet reactivity (HPR) as compared to ticagrelor, even if 600 mg clopidogrel LD was given . These pharmacodynamic data support our findings.…”

“…Despite the superior pharmacodynamic effects and clinical efficacy outcomes of ticagrelor over clopidogrel, switching between the two is common in patients with STEMI . The modalities of switching are defined as de‐escalation and escalation . In China, switching from ticagrelor to clopidogrel, which is defined as de‐escalation, after PCI is more common.…”

2018 ESC/EACTS Guidelines on myocardial revascularization

“…716 Based on recent results from the randomized TROPICAL-ACS (Testing responsiveness to platelet inhibition on chronic antiplatelet treatment for acute coronary syndromes) trial 717 , an approach of DAPT de-escalation guided by platelet function testing may be considered in ACS patients (NSTE-ACS and STEMI) as an alternative to 12 months potent platelet inhibition, especially for patients deemed unsuitable for maintained potent platelet inhibition. For a more detailed description of the pertinent clinical trials in the field of DAPT duration and switching antiplatelet drugs, we refer the reader to the International Expert Consensus document on Switching Platelet P2Y12 Receptor-Inhibiting Therapies 718 and the 2017 ESC Focused Update on Dual Antiplatelet Therapy in Coronary Artery Disease. 410 Following DAPT, lifelong single antiplatelet therapy (usually with aspirin) is recommended and patients should be advised not to prematurely discontinue oral antiplatelet therapy after stenting.…”

The occurrence of neointimal hyperplasia after flow-diverter implantation is associated with cardiovascular risks factors and the stent design

“…The pharmacodynamic effects of ticagrelor are more prompt, potent, and predictable compared with those of clopidogrel 24. It has been linked to inhibition of SMC proliferation and, hence, could be associated with reduced NIH 25.…”