What are P2Y12 (Purinergic Receptor P2Y12) inhibitors?

From the Guidelines

P2Y12 inhibitors are a class of antiplatelet medications that play a crucial role in preventing blood clots in patients with acute coronary syndrome, particularly those undergoing percutaneous coronary intervention (PCI) or with a history of myocardial infarction, with the most recent guidelines recommending their use in addition to aspirin for at least 12 months unless contraindicated or if there's an excessive risk of bleeding 1.

Overview of P2Y12 Inhibitors

P2Y12 inhibitors are primarily used to prevent thrombotic events in patients with acute coronary syndromes. The main P2Y12 inhibitors include clopidogrel (Plavix), prasugrel (Effient), and ticagrelor (Brilinta). These medications work by blocking the P2Y12 receptor on platelets, preventing ADP from binding and initiating the platelet aggregation cascade, which is a key step in the formation of blood clots.

Dosage and Administration

• Clopidogrel is typically dosed at 75mg daily with a 300-600mg loading dose.
• Prasugrel is dosed at 10mg daily with a 60mg loading dose.
• Ticagrelor is dosed at 90mg twice daily with a 180mg loading dose. These medications are usually prescribed alongside aspirin as dual antiplatelet therapy (DAPT), with the treatment duration depending on the clinical scenario and bleeding risk.

Safety Considerations

• Prasugrel is contraindicated in patients with a history of stroke or transient ischemic attack (TIA) and should be used cautiously in patients over 75 years or under 60kg due to an increased risk of bleeding 1.
• Ticagrelor may cause dyspnea and requires twice-daily dosing.
• The choice of P2Y12 inhibitor and the duration of therapy should be individualized based on the patient's risk of ischemic events and bleeding.

Clinical Guidelines

The most recent European Society of Cardiology (ESC) guidelines from 2020 recommend a P2Y12 receptor inhibitor in addition to aspirin for patients with non-ST-elevation acute coronary syndrome (NSTE-ACS), to be maintained over 12 months unless there are contraindications or an excessive risk of bleeding 1. This recommendation highlights the importance of P2Y12 inhibitors in the management of acute coronary syndromes and emphasizes the need for careful patient selection and monitoring to minimize the risk of adverse effects, particularly bleeding.

From the FDA Drug Label

P2Y12 inhibitors (thienopyridines), including clopidogrel, increase the risk of bleeding. Prasugrel is a thienopyridine class inhibitor of platelet activation and aggregation mediated by the P2Y12 ADP receptor

P2Y12 inhibitors are a class of drugs that inhibit platelet activation and aggregation by binding to the P2Y12 ADP receptor on platelets. They include drugs such as clopidogrel and prasugrel, which are used to reduce the risk of myocardial infarction and stroke in patients with acute coronary syndrome or established peripheral arterial disease. These drugs increase the risk of bleeding due to their mechanism of action, which irreversibly inhibits platelet aggregation for the lifetime of the platelet (7 to 10 days) 2 3.

• Key characteristics:
  • Inhibit platelet activation and aggregation
  • Bind to the P2Y12 ADP receptor on platelets
  • Increase the risk of bleeding
  • Include drugs such as clopidogrel and prasugrel
  • Used to reduce the risk of myocardial infarction and stroke in patients with acute coronary syndrome or established peripheral arterial disease

From the Research

Definition and Function of P2Y12 Inhibitors

• P2Y12 inhibitors are a class of antiplatelet drugs that play a crucial role in preventing blood clots in patients with acute coronary syndrome (ACS) 4, 5, 6, 7, 8.
• They work by inhibiting the P2Y12 receptor on platelets, which helps to prevent platelet activation and aggregation, thereby reducing the risk of thrombosis 4, 5, 6, 7, 8.

Types of P2Y12 Inhibitors

• There are several types of P2Y12 inhibitors available, including clopidogrel, prasugrel, and ticagrelor 4, 5, 6, 7, 8.
• Clopidogrel is an older generation P2Y12 inhibitor, while prasugrel and ticagrelor are newer and more potent inhibitors 4, 5, 6, 7, 8.
• Ticagrelor is a reversible P2Y12 inhibitor, which means it can bind to and release from the P2Y12 receptor, allowing for more flexible dosing and potentially fewer side effects 5.

Clinical Use of P2Y12 Inhibitors

• P2Y12 inhibitors are commonly used in combination with aspirin as dual antiplatelet therapy (DAPT) to reduce the risk of cardiovascular events in patients with ACS 4, 5, 6, 7, 8.
• The choice of P2Y12 inhibitor and duration of therapy depends on individual patient characteristics, such as bleeding risk and ischemic risk 4, 6, 8.
• Guided selection of P2Y12 inhibiting therapy using platelet function or genetic testing may improve outcomes in patients with ACS 8.

Efficacy and Safety of P2Y12 Inhibitors

• P2Y12 inhibitors have been shown to reduce the risk of major adverse cardiovascular events (MACE) and stent thrombosis in patients with ACS 4, 5, 6, 7, 8.
• However, they also increase the risk of bleeding, particularly major bleeding 4, 6, 8.
• Prasugrel and ticagrelor have been shown to be more efficacious than clopidogrel, but also have a higher risk of bleeding 4, 6, 8.
• A guided approach to selecting P2Y12 inhibiting therapy may help to balance efficacy and safety in patients with ACS 8.