From the Guidelines
For a PGY-2 hyporesponder to clopidogrel (Plavix), I recommend switching to ticagrelor (Brilinta) 90 mg twice daily, as it has been shown to significantly reduce the primary cardiovascular endpoint and all-cause mortality compared to clopidogrel, with no differences in major bleeding events, as demonstrated in the PLATO trial 1. When switching, give the loading dose of ticagrelor (180 mg) 24 hours after the last clopidogrel dose. Ticagrelor requires twice-daily dosing but doesn't need genetic activation like clopidogrel.
- Key considerations for ticagrelor include:
- Twice-daily dosing
- No need for genetic activation
- Potential for dyspnea in some patients, which is typically mild but may require switching to prasugrel if intolerable
- Increased bleeding risk, particularly in patients with renal impairment, low body weight, or those on concomitant anticoagulants
- According to the 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for the management of patients with acute coronary syndromes, ticagrelor is a recommended alternative to clopidogrel for patients with ACS, including those with renal impairment 1.
- It is essential to monitor patients for increased bleeding risk and adjust the treatment plan accordingly, taking into account the patient's individual risk factors and medical history.
From the FDA Drug Label
Consider use of another platelet P2Y 12inhibitor in patients identified as CYP2C19 poor metabolizers. The patient is a PGY-2 hyporesponder, which means they have a reduced response to clopidogrel.
- The FDA drug label for clopidogrel suggests considering the use of another platelet P2Y12 inhibitor in patients identified as CYP2C19 poor metabolizers.
- Prasugrel is another platelet P2Y12 inhibitor that can be considered as an alternative to clopidogrel.
- The decision to change from clopidogrel to another antiplatelet should be based on the individual patient's response to treatment and their genetic profile, specifically their CYP2C19 genotype 2.
From the Research
PGY-2 Hyporesponder Management
The management of patients who are hyporesponders to clopidogrel, such as those with a poor response to Plavix, is a complex issue.
- The use of alternative antiplatelet agents, such as prasugrel or ticagrelor, may be considered in patients who are poor responders to clopidogrel 3, 4, 5.
- These agents have been shown to be more effective than clopidogrel in reducing cardiovascular events in certain patient populations 4, 5.
- However, they may also increase the risk of bleeding in some patients 4, 5.
Alternative Antiplatelet Agents
Some alternative antiplatelet agents that may be used in patients who are poor responders to clopidogrel include:
- Prasugrel: a thienopyridine antiplatelet agent that has been shown to be more effective than clopidogrel in reducing cardiovascular events in patients undergoing percutaneous coronary intervention (PCI) 4, 5.
- Ticagrelor: a cyclopentyltriazolopyrimidine antiplatelet agent that has been shown to be more effective than clopidogrel in reducing cardiovascular events in patients with acute coronary syndromes 6, 4.
- Glycoprotein IIb/IIIa inhibitors: a class of antiplatelet agents that may be used in patients undergoing PCI, particularly in those who are poor responders to clopidogrel 6, 7.
Considerations for Management
When managing a patient who is a poor responder to clopidogrel, several factors should be considered, including:
- The patient's individual risk factors for cardiovascular events and bleeding 4, 5.
- The potential benefits and risks of alternative antiplatelet agents 4, 5.
- The use of point-of-care assays to assess platelet function and guide therapy 5.
- The potential for drug-drug interactions and the need for careful monitoring of the patient's medication regimen 3, 5.