Clopidogrel and Tigretol are both P2Y12 receptor inhibitors, so they cannot be combined, so how should the clinic choose? Today, we will sort it out for you ~
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What is the difference in dosage?
Clopidogrel is a P2Y12 receptor antagonist, which is an inactive precursor drug and needs to be activated by the liver. It effectively reduces ADP-mediated platelet activation and aggregation by selectively and irreversibly inhibiting platelet ADP receptors and blocking P2Y12-dependent activation of the platelet membrane glycoprotein (GP) IIb/IIIa complex.
The half-Life is 6 hours, and the onset of action is 2 to 8 hours at regular doses. It is mainly used in patients with recent myocardial infarction, in combination with aspirin in patients with ACS (including after stenting), for The prevention of atherosclerotic thrombotic events and in patients for whom aspirin is contraindicated.
Dosage
Non-ST-segment elevation acute coronary syndrome: oral, single loading dose of 300 mg, followed by 75 mg qd, recommended in combination with aspirin, not to exceed 100 mg/day.
Acute ST-segment elevation myocardial infarction: no loading dose over 75 years of age, at least 4 weeks of dosing
After coronary drug stenting: 75 mg qd po for at least 1 year, recommended in combination with aspirin.
Tegretol is a new P2Y12 receptor antagonist, a non-precursor drug that acts directly on platelet ADP receptors without hepatic activation. It has an onset of action from 30 minutes to 4 hours at regular doses, with a mean half-life of 7.2 hours.
Compared to clopidogrel, it is characterized by its rapid onset of action and strong and reversible antiplatelet effect. Therefore, platelet transfusions are the only option when platelet counts drop with clopidogrel, whereas platelets can recover on their own after tigretol is discontinued.
Dosage
Tegretol is recommended for patients with STEMI who are at high risk for ischemia and have a propensity for clopidogrel resistance to intravenous thrombolysis. It is administered orally at a loading dose of 180 mg and a maintenance dose of 90 mg bid in patients with ACS and 60 mg bid in patients 1 year after high-risk myocardial infarction.
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How is the clinical dose chosen?
Based on the benefits of tegretol therapy for patients with ACS, domestic and international guidelines recommend tegretol for antiplatelet therapy in patients with ACS.
Several authoritative ESC guidelines (2015 ESC NSTE-ACS guidelines, 2017 STEMI guidelines, 2017 DAPT guidelines) state that clopidogrel should only be considered in patients who are intolerant to tigretol therapy.
The results of the PLATO study showed that 12 months of tigrigrelol treatment further significantly reduced the risk of cardiovascular death, myocardial infarction, and stroke as a composite endpoint event compared to clopidogrel in patients with ACS without increasing major bleeding, while significantly reducing the risk of cardiovascular death.
In patients undergoing PCI after post-thrombolytic transfer for STEMI, the platelet inhibition effect of pre-PCI use of tigretol was superior to that of clopidogrel.
For patients with ACS at relatively high risk of thrombotic events, such as diabetes, chronic kidney disease, and complex coronary artery disease, tegretol (loading dose 180 mg, maintenance dose 90 mg bid) in combination with aspirin for at least 12 months is preferred for antiplatelet therapy.
In the study, STEMI patients <75 years of age were randomized to receive a loading dose of tegretol 180 mg or clopidogrel 300 mg within 24 h after intravenous thrombolysis, followed by a maintenance dose, respectively.
The risk of major bleeding was noninferior to that of the clopidogrel group within 30 d, but the proportion of minor bleeding was higher in the tigrilol group than in the clopidogrel group.
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Therefore, it is recommended that in patients at high risk of ischemia requiring potent antiplatelet agents and in STEMI patients with clopidogrel-resistant tendency for intravenous thrombolysis, a loading dose of tigretol of 180 mg on top of aspirin and a maintenance dose of 90 mg bid if they are <75 years of age.
If age ≥ 75 years, clopidogrel 75 mg with a maintenance dose of 75 mg qd.
3
Precautions
Dose change recommendations
Patients with ACS who are already receiving a loading dose of clopidogrel and need to switch to tigrilol may be given an initial loading dose of 180 mg with a maintenance dose of 90 mg bid without increased risk of bleeding.
Switching from tigrilol to clopidogrel is not recommended unless there is a serious adverse reaction or bleeding, and if a switch is required, a loading dose of 300-600 mg is recommended in the absence of bleeding.
The PLATO study has demonstrated that the long-term prognosis of patients treated with tigretol is better than that of clopidogrel. From a pharmacoeconomic perspective, the use of tigrigrelol in Chinese ACS patients has a better cost-effectiveness compared to clopidogrel.
Countermeasures for missed doses
Missed doses should be avoided as much as possible during tegretol therapy. One missed dose does not affect the antiplatelet effect and does not need to be replaced.
The TWICE study demonstrated that 24-h IPA (platelet aggregation inhibition rate) was still higher in patients taking 2 doses/d of tegretol than in patients taking continuous clopidogrel; 1-d missed dose of tegretol (2 consecutive missed doses) resulted in IPA values comparable to those of 1-d missed dose of clopidogrel.
Combination with PPI
PPIs are often used in combination with dual antiplatelet therapy in patients with ACS to reduce the risk of gastrointestinal bleeding.
It has been suggested that some PPIs may reduce the antiplatelet efficacy of clopidogrel because both clopidogrel and PPIs are metabolized via CYP2C19, and PPIs may competitively inhibit the effects of clopidogrel.
Tegretol, however, is a non-precursor drug that does not undergo the CYP2C19 enzyme metabolic pathway and does not significantly affect the pharmacokinetics of tegretol when combined with a PPI.
PLATO and its subgroup studies also confirmed that the combination of tegretol with PPI did not affect its antiplatelet efficacy, and the combination was reasonable and safe.
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