Reduced Variability to Aspirin Antiplatelet Effect by the Coadministration of Statins in High-Risk Patients for Cardiovascular Disease

Autor: Alessandra Meneguzzi, L. Grossi, Luigia Di Francesco, Annalisa Bruno, Ettore Porreca, Patrizia Ballerini, Stefano Manarini, Cristiano Fava, Giacomo Levantesi, Paola Patrignani, Concetta Di Febbo, Marta L. Capone, Melania Dovizio, Virgilio Evangelista, Pietro Minuz, Stefania Tacconelli, Ilaria D'Agostino
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Thromboxane
Atorvastatin
thromboxane A2
030204 cardiovascular system & hematology
Gastroenterology
Thromboxane A2
chemistry.chemical_compound
0302 clinical medicine
Risk Factors
cardiovascular disease
Secondary Prevention
MRP4
cyclooxygenase-1
low-dose aspirin
platelets
statins
Medicine
Pharmacology (medical)
Platelet
Aspirin
Acetylation
Middle Aged
Primary Prevention
Thromboxane B2
Cardiovascular Diseases
Platelet aggregation inhibitor
Drug Therapy
Combination
Female
lipids (amino acids
peptides
and proteins)
Tablets
Enteric-Coated
medicine.drug
Blood Platelets
medicine.medical_specialty
Statin
medicine.drug_class
Biological Availability
In Vitro Techniques
03 medical and health sciences
Internal medicine
Humans
Aged
Pharmacology
business.industry
030104 developmental biology
chemistry
Cyclooxygenase 1
Hydroxymethylglutaryl-CoA Reductase Inhibitors
business
Platelet Aggregation Inhibitors
Zdroj: Clinical Pharmacology & Therapeutics. 104:111-119
ISSN: 0009-9236
DOI: 10.1002/cpt.1075
Popis: We studied the influence of cardiovascular (CV) risk factors, previous CV events, and cotreatments with preventive medicines, on residual platelet thromboxane (TX)B2 production in 182 patients chronically treated with enteric coated (EC)-aspirin (100 mg/day). The response to aspirin was also verified by assessing arachidonic acid-induced platelet aggregation and urinary 11-dehydro-TXB2 levels. Residual serum TXB2 levels exceeded the upper limit value for an adequate aspirin response in 14% of individuals. This phenomenon was detected at 12 hours after dosing with aspirin. The coadministration of statins (mostly atorvastatin) was an independent predictor of residual serum TXB2 levels, and the percentage of patients with enhanced values was significantly lower in statin users vs. nonusers. We provide evidence in vitro that atorvastatin reduced residual TXB2 generation by increasing the extent of acetylation of platelet COX-1 by aspirin. In conclusion, the coadministration of statins may counter the mechanisms associated with reduced bioavailability of aspirin detected in some individuals with CV disease.
Databáze: OpenAIRE
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