Loading Dose Requirements When Switching from Plavix to Brilinta
When switching a patient from Plavix (clopidogrel) to Brilinta (ticagrelor), a loading dose of 180 mg of Brilinta is recommended regardless of the timing and previous loading dose of clopidogrel.
Evidence-Based Rationale
The European Society of Cardiology (ESC) provides clear guidance on this matter with a Class I recommendation and Level B evidence. According to the 2018 ESC guidelines on dual antiplatelet therapy in coronary artery disease:
- "In patients with ACS who were previously exposed to clopidogrel, switching from clopidogrel to ticagrelor is recommended early after hospital admission at a loading dose of 180 mg irrespective of timing and loading dose of clopidogrel, unless contraindications to ticagrelor exist" 1.
Pharmacological Considerations
The recommendation for a loading dose is based on several important pharmacological principles:
Different Mechanisms of Action: While both are P2Y12 inhibitors, ticagrelor is a direct-acting reversible inhibitor, whereas clopidogrel is a prodrug requiring hepatic conversion to its active metabolite.
Onset of Action: Ticagrelor has a more rapid onset and more pronounced platelet inhibition than clopidogrel 2, 3. The loading dose ensures quick achievement of therapeutic antiplatelet effect.
Displacement from Receptor Sites: The loading dose helps ticagrelor effectively displace clopidogrel from platelet receptors, ensuring optimal platelet inhibition without delay.
Clinical Implications
The PLATO trial demonstrated that ticagrelor achieves greater antiplatelet effect than clopidogrel in patients with acute coronary syndromes, both in the first hours of treatment and during maintenance therapy 2. This superior platelet inhibition translates to clinical benefits:
- Reduced rate of death from vascular causes, myocardial infarction, or stroke (9.8% with ticagrelor vs. 11.7% with clopidogrel) 3
- Reduced all-cause mortality (4.5% with ticagrelor vs. 5.9% with clopidogrel) 3
Maintenance Dosing After Switch
After administering the 180 mg loading dose of ticagrelor:
- Continue with the standard maintenance dose of 90 mg twice daily 4
- Ensure the patient is also taking low-dose aspirin (75-100 mg daily) 4
Special Considerations
Bleeding Risk: While ticagrelor provides superior efficacy, it may be associated with higher non-CABG related bleeding compared to clopidogrel 3. In elderly patients (≥70 years) with NSTE-ACS, clopidogrel may be a favorable alternative due to fewer bleeding events 5.
Dyspnea: Ticagrelor is associated with dyspnea in some patients, which may lead to discontinuation 4. Patients should be informed about this potential side effect.
Timing: The switch should ideally be made early after hospital admission for ACS patients 1.
Conclusion
When transitioning from clopidogrel to ticagrelor, a loading dose of 180 mg ticagrelor is necessary regardless of previous clopidogrel dosing to ensure optimal platelet inhibition and clinical outcomes.