From the Guidelines
Yes, you should still administer the standard loading dose of ticagrelor (180 mg) in patients with mild to moderate hepatic impairment. No dose adjustment is required for these patients. Ticagrelor is primarily metabolized by the liver via CYP3A4 enzymes, but clinical studies have shown that mild to moderate hepatic impairment does not significantly alter the drug's pharmacokinetics or antiplatelet effects to a degree that would necessitate dose modification. However, ticagrelor is contraindicated in patients with severe hepatic impairment (Child-Pugh class C) due to limited data and potential risk of increased exposure. When administering ticagrelor to patients with hepatic impairment, it's essential to monitor for bleeding complications, as is standard practice with all antiplatelet therapies. The maintenance dose following the loading dose should remain at the standard 90 mg twice daily for most indications, unless other clinical factors suggest a different maintenance regimen is appropriate 1.
Some key points to consider:
- The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily 1.
- Ticagrelor's benefits were observed irrespective of prior therapy with clopidogrel 1.
- When possible, discontinue ticagrelor at least 5 days before any surgery 1.
- Issues of patient compliance may be especially important with twice-daily dosing regimen 1.
- Consideration should be given to the potential and as yet undetermined risk of intracranial hemorrhage in patients with prior stroke or TIA 1.
From the Research
Ticagrelor Loading Dose in Patients with Mild to Moderate Hepatic Impairment
- The study 2 found that mild hepatic impairment resulted in modestly higher exposure to ticagrelor and its active metabolite, without subsequent effects on pharmacodynamics or tolerability, suggesting that no ticagrelor dosage adjustment is needed in patients with mild hepatic impairment.
- Another study 3 reported that no dose adjustment for ticagrelor is required on the basis of age, gender, ethnicity, severe renal impairment, or mild hepatic impairment.
- However, the study 4 found that a 180-mg loading dose regimen of ticagrelor is associated with more potent and prompt platelet inhibition compared with a 90-mg maintenance dose, but it did not specifically address patients with hepatic impairment.
- There is no direct evidence from the provided studies that addresses the use of a loading dose of ticagrelor in patients with mild to moderate hepatic impairment.
- Studies 5 and 6 do not provide relevant information on ticagrelor loading dose in patients with hepatic impairment, as they focus on different topics, such as milvexian pharmacokinetics and platelet reactivity during ticagrelor maintenance therapy, respectively.
Key Findings
- Ticagrelor exposure is higher in patients with mild hepatic impairment, but this does not affect pharmacodynamics or tolerability 2.
- No dose adjustment is needed for ticagrelor in patients with mild hepatic impairment 2, 3.
- A loading dose of ticagrelor may be beneficial for achieving prompt platelet inhibition, but its use in patients with hepatic impairment is not specifically addressed in the provided studies 4.