Will changing Plavix (clopidogrel) to a different antiplatelet agent improve response in a postgraduate year 2 (PGY-2) patient with hyporesponsiveness to antiplatelet therapy?

From the Guidelines

For a PGY-2 hyporesponder to clopidogrel (Plavix), I recommend switching to ticagrelor (Brilinta) 90mg 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 from clopidogrel, administer a loading dose of ticagrelor 180mg once, then continue with maintenance dosing. No washout period is needed when transitioning directly from clopidogrel. Ticagrelor is a more potent P2Y12 inhibitor with more predictable pharmacodynamics and less genetic variability in metabolism compared to clopidogrel. Approximately 30% of patients have genetic polymorphisms in CYP2C19 that reduce clopidogrel's effectiveness, as it requires hepatic conversion to its active metabolite. Ticagrelor has more consistent antiplatelet effects but carries an increased bleeding risk, so assess the patient's bleeding risk before switching. Continue aspirin therapy as prescribed unless contraindicated, and monitor for bleeding complications after the switch.

• Key considerations when switching to ticagrelor include:
  • Increased risk of bleeding, particularly non-CABG major bleeding
  • Potential for subjective transient dyspnea in approximately 10% to 15% of patients
  • Need for careful assessment of bleeding risk before switching
  • Importance of continuing aspirin therapy as prescribed unless contraindicated
  • Monitoring for bleeding complications after the switch, as recommended in the 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for the management of patients with acute coronary syndromes 1.

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 2.
• Prasugrel is another platelet P2Y12 inhibitor that can be considered as an alternative to clopidogrel 3. Therefore, changing plavix (clopidogrel) to a different antiplatelet such as prasugrel may be a suitable option for this patient.

From the Research

PGY-2 Hyporesponder Management

• Changing antiplatelet therapy is a consideration for patients who are hyporesponders to clopidogrel, such as PGY-2 patients 4.
• The management of poor responders to clopidogrel is challenging, but strategies such as increasing the maintenance dose or switching to a different thienopyridine (e.g., ticlopidine or prasugrel) or using glycoprotein IIb/IIIa inhibitors during PCI may be helpful 4.
• Platelet function tests can identify patients who are resistant to clopidogrel, and intensifying antiplatelet therapy to achieve ≥20% inhibition on platelet function testing may not result in higher numbers of ischemic or hemorrhagic events, but there is a trend toward more death in the resistant group by 30 and 90 days of those experiencing complications 5.

Switching Antiplatelet Therapy

• Switching between P2Y12 inhibitors (e.g., clopidogrel, prasugrel, ticagrelor) is possible, and several pharmacodynamic studies have provided information on how to change drugs without impairing platelet inhibition 6.
• The use of glycoprotein IIb/IIIa inhibitors does not impact the relative efficacy and safety of ticagrelor compared with clopidogrel in patients with acute coronary syndromes undergoing PCI 7.
• Reversing the antiplatelet effect of P2Y12 receptor inhibitors may be necessary in certain clinical scenarios, such as active severe bleeding or urgent procedures with high bleeding risk, and supplementation of platelets or administration of a monoclonal antibody fragment (e.g., PB2452) may be effective in reversing platelet inhibition 8.

Considerations for PGY-2 Hyporesponders

• For PGY-2 hyporesponders, changing from clopidogrel to a different antiplatelet agent, such as prasugrel or ticagrelor, may be considered based on individual patient factors and clinical scenarios 4, 5, 6.
• The decision to switch antiplatelet therapy should be made on a case-by-case basis, taking into account the patient's medical history, current medications, and potential risks and benefits of switching therapy 4, 5, 6.