The following are key points to remember about this international expert consensus document on switching platelet P2Y₁₂ receptor-inhibiting therapies:

1. Dual antiplatelet therapy with aspirin and a P2Y₁₂ 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.
2. The availability of different oral P2Y₁₂ inhibitors (clopidogrel, prasugrel, ticagrelor) and an intravenous P2Y₁₂ inhibitor (cangrelor) has led physicians to contemplate switching among therapies because of a variety of factors. This expert consensus provides an overview of the pharmacology of P2Y₁₂ inhibitors, different modalities and definitions of switching, and available literature and recommendations for switching between P2Y₁₂ inhibitors. The timing of switching with respect to the duration since the initiating event may be defined as acute (<24 hours), early (1–30 days), late (>30 days–1 year), or very late (>1 year).
3. Escalation from clopidogrel to prasugrel or ticagrelor in the early, particularly acute phase of treatment, should occur with the use of a 60- or 180-mg loading dose (LD), respectively. Administration of an LD regimen may occur regardless of the timing of the last dose of clopidogrel. This should be followed by standard maintenance dose (MD) regimens (prasugrel 10 mg daily or ticagrelor 90 mg twice-daily).
4. Beyond the early phase, it is reasonable to escalate with a 10-mg daily or 90-mg twice-daily MD regimen of prasugrel or ticagrelor, respectively, without an LD. It is also reasonable and practical for the patient to start the new MD regimen at the time of the next scheduled dose of P2Y₁₂-inhibiting therapy (e.g., approximately 24 hours from last dose of clopidogrel).
5. There was a lack of group consensus on the appropriate approach to de-escalate from prasugrel to clopidogrel in the acute/early phase (i.e., with an MD or an LD) given the limited data on therapy de-escalation. In the early and, in particular, the acute phases of de-escalation, it also may be reasonable to administer a 600-mg LD of clopidogrel. Beyond the early phase or in more stabilized patients, the use of a 75-mg MD of clopidogrel (without an LD) at the time of the next scheduled dose (e.g., approximately 24 hours from last dose of prasugrel) should be considered.
6. Because ticagrelor has a relatively fast offset of action, the use of a clopidogrel 600-mg LD should be considered when de-escalating from ticagrelor to avoid any significant gap in platelet inhibition, regardless of the timing of switching (i.e., acute, early, or late). However, de-escalation to clopidogrel with an MD is a reasonable option, particularly in patients in whom switching occurs as a result of bleeding.
7. On the basis of pharmacodynamic data suggesting a potential drug-drug interaction (DDI), a 60-mg LD of prasugrel should always be used when changing from ticagrelor to prasugrel, regardless of timing (early or late), and switching with a 10-mg MD should be avoided. Pharmacodynamic studies do not suggest DDI when changing from prasugrel to ticagrelor therapy. Therefore, this change can be performed with a standard 90-mg twice-daily MD dose regimen, without the need for an LD.
8. Because the effects of the oral agents persist with meaningful levels of P2Y₁₂ inhibition after drug discontinuation, it is reasonable to wait to start cangrelor bridging (0.75 μg·kg⁻¹·min⁻¹ infusion without a bolus) for up to 3-4 days after prasugrel discontinuation and 2-3 days of clopidogrel and ticagrelor discontinuation to minimize the duration of infusion. In the transition from cangrelor to a thienopyridine, the thienopyridine should be administered immediately after discontinuation of cangrelor with an LD (clopidogrel 600 mg or prasugrel 60 mg) to avoid a potential DDI.
9. After noncardiac surgery, regardless of bridging strategy, clopidogrel should be resumed with an LD as soon as oral administration is possible and the risk of severe bleeding is acceptable. Prasugrel and ticagrelor administration should be discouraged in the early period after major noncardiac surgery when there is an ongoing risk of serious bleeding.
10. These recommendations are derived largely from pharmacodynamic and registry data, integrated with an understanding of the pharmacological principles of the agents involved. Dedicated prospective studies are needed to provide important insights into this topic.

Keywords: Acute Coronary Syndrome, Adenosine, Aspirin, Blood Platelets, Consensus, Drug Interactions, Hemorrhage, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Receptors, Purinergic P2Y12, Secondary Prevention, Thrombosis, Ticlopidine, Vascular Diseases

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