Antiplatelet effect of clopidogrel in patients with aspirin therapy undergoing percutaneous coronary interventions – Limited inhibition of the P2Y12 receptor
| Autor: | Aino Lepäntalo, Jussi Mikkelsson, Julio C. Reséndiz, Leena E. Viiri, Kari S. Virtanen, Pekka J. Karhunen, Riitta Lassila |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Blood Platelets Male Ticlopidine Platelet Aggregation medicine.drug_class Pharmacology chemistry.chemical_compound Cangrelor P2Y12 Purinergic P2 Receptor Antagonists Humans Medicine Platelet cardiovascular diseases Platelet activation Angioplasty Balloon Coronary Aged Aged 80 and over Aspirin Dose-Response Relationship Drug business.industry Hematology Middle Aged Receptor antagonist Clopidogrel Adenosine Monophosphate Thromboxane B2 Treatment Outcome chemistry Anesthesia Drug Therapy Combination Female business Platelet Aggregation Inhibitors circulatory and respiratory physiology medicine.drug |
| Zdroj: | Thrombosis Research. 124:193-198 |
| ISSN: | 0049-3848 |
| DOI: | 10.1016/j.thromres.2009.01.009 |
| Popis: | Introduction Large individual variability in clopidogrel responses has been reported. However, mechanisms of the non-responsiveness are unclear. Our aim was to study the extent of platelet inhibition at the receptor level by in vitro receptor antagonists of P2Y 12 (AR-C69931MX, cangrelor) and P2Y 1 (adenosine 3’,5’diphosphate) in aspirin treated patients with coronary artery disease (CAD) prior to and after in vivo clopidogrel. Materials and Methods 51 aspirin-treated (100 mg/day) patients participated. Blood was collected before and after administration of clopidogrel at 300 mg loading dose on day one, followed by 75 mg/d for four days. Aggregation in platelet-rich plasma was assessed. Results In 20% of patients clopidogrel failed to inhibit platelet responses to ADP. These non-responders had also decreased sensitivity to an in vitro P2Y 12 -receptor antagonist compared with the responders (mean inhibition of aggregation 25 vs. 32%, difference of means 7% (95% CI 2-12%), P 12 -receptor inhibition by in vivo clopidogrel correlated with the inhibition by in vitro ARMX measured prior to administration of clopidogrel. Neither P2Y 1 -receptor activity, thrombin generation while on aspirin nor basal platelet activity associated with clopidogrel responses. Conclusions Concomitant aspirin and clopidogrel treatment failed to suppress platelet activity in 20% of patients. Non-responders to clopidogrel had decreased responses also to another ADP receptor antagonist, which suggests that the impaired response occurs at the level of P2Y 12 -receptor. |
| Databáze: | OpenAIRE |
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