Clinical and Pharmacological Parameters Determine Relapse During Clopidogrel Treatment of Acute Coronary Syndrome.

Abstract

The therapeutic efficacy of clopidogrel as an antiplatelet drug varies among individuals, being the mainstream hypothesis that its bioavailability depends on the individual genetic background and/or interactions with other drugs. A total of 477 patients receiving double antiaggregation therapy with aspirin and clopidogrel, after suffering a first event, were followed for 1 year to record relapse, as a surrogate end point to measure their therapeutic response, as defined by presenting with an acute coronary event (unstable angina, ST-segment-elevation myocardial infarction, or non-ST-segment-elevation myocardial infarction), stent thrombosis/restenosis, or cardiac mortality. Anthropometric, clinical, and pharmacological variables along with CYP2C19 genotypes were analyzed for their association with the disease relapse phenotype. Only 75 patients (15%) suffered a relapse, which occurred during the first 6 months of therapy, with a peak at 4.5 months. An initial univariate analysis identified that patients in the relapse group were significantly older (67.4 ± 11.0 vs 61.6 ± 12.3 years old) and presented with diffuse coronary disease, insulin-dependent type 2 diabetes mellitus dyslipidemia, and arterial hypertension. A poor clinical response to the platelet antiaggregation regime also occurred more frequently among patients taking acenocoumarol and calcium channel blockers, along with aspirin and clopidogrel, while no association was found according to CYP2C19 genotypes. A retrospective multivariate analysis indicated that patients belonging to the nonresponder phenotype to treatment with aspirin and clopidogrel were older, presented with diffuse coronary disease, a group largely overlapping with type 2 insulin-dependent diabetes mellitus, and were taking dihidropyrimidinic calcium channel blockers.

• Authors: Marta Santana-Mateos, José M Medina-Gil, Pedro Saavedra-Santana, Efrén Martínez-Quintana, Fayna Rodríguez-González, Antonio Tugores
• Journal: Journal of clinical pharmacology (J Clin Pharmacol) Vol. 62 Issue 6 Pg. 783-791 (06 2022) ISSN: 1552-4604 [Electronic] England
• PMID: 34958683 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021, The American College of Clinical Pharmacology.

Chemical References

• Calcium Channel Blockers
• Platelet Aggregation Inhibitors
• Clopidogrel
• Cytochrome P-450 CYP2C19
• Ticlopidine
• Aspirin

Topics

• Acute Coronary Syndrome (drug therapy)
• Aspirin (therapeutic use)
• Calcium Channel Blockers (therapeutic use)
• Clopidogrel (therapeutic use)
• Coronary Artery Disease
• Cytochrome P-450 CYP2C19 (genetics)
• Diabetes Mellitus, Type 2 (drug therapy)
• Humans
• Myocardial Infarction (drug therapy)
• Platelet Aggregation Inhibitors
• Recurrence
• Retrospective Studies
• Ticlopidine (therapeutic use)
• Treatment Outcome