Association of Cyclooxygenase-1-Dependent and -Independent Platelet Function Assays With Adverse Clinical Outcomes in Aspirin-Treated Patients Presenting for Cardiac Catheterization
| Autor: | Andrew L. Frelinger, YouFu Li, Marc R. Barnard, Marsha L. Fox, Mark I. Furman, Douglas J. Christie, Matthew D. Linden, Alan D. Michelson |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Blood Platelets Male Cardiac Catheterization medicine.medical_specialty Thromboxane medicine.medical_treatment Drug Resistance Coronary Artery Disease Kaplan-Meier Estimate Revascularization chemistry.chemical_compound Predictive Value of Tests Physiology (medical) Internal medicine medicine Humans Platelet Prospective Studies Myocardial infarction Cardiac catheterization Aspirin business.industry Percutaneous coronary intervention Middle Aged medicine.disease Thromboxane B2 P-Selectin Treatment Outcome chemistry Anesthesia Cyclooxygenase 1 Cardiology Female Collagen Cardiology and Cardiovascular Medicine business Platelet Aggregation Inhibitors medicine.drug |
| Zdroj: | Circulation. 120:2586-2596 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circulationaha.109.900589 |
| Popis: | Background— Poor clinical outcome in aspirin-treated patients has been termed aspirin resistance and may result from inadequate inhibition of platelet cyclooxygenase-1 (COX-1) by aspirin. The objectives of this study were to determine prospectively whether COX-1-dependent and other platelet function assays correlate with clinical outcomes in aspirin-treated patients. Methods and Results— Blood was collected before percutaneous coronary intervention from 700 consecutive aspirin-treated (81 or 325 mg for ≥3 days) patients. Platelet function was tested by (1) serum thromboxane B 2 ; (2) arachidonic acid-stimulated platelet surface P-selectin and activated glycoprotein IIb/IIIa and leukocyte-platelet aggregates; and (3) platelet function analyzer (PFA)-100 collagen-epinephrine and collagen-ADP closure time (CT). Adverse clinical outcomes of all-cause death, cardiovascular death, and major adverse cardiovascular events (cardiovascular death, myocardial infarction, hospitalization for revascularization, or acute coronary syndrome) were assessed by telephone interview and/or medical record review. Clinical outcomes information was obtained at 24.8±0.3 months after platelet function testing. By univariate analysis, COX-1-dependent assays, including serum thromboxane B 2 level, were not associated with adverse clinical outcomes, whereas the COX-1-independent assay, PFA-100 collagen-ADP CT P =0.0149). After adjustment for covariables (including sex, aspirin dose, Thrombolysis in Myocardial Infarction risk score, clopidogrel use), both serum thromboxane B 2 >3.1 ng/mL and PFA-100 collagen-ADP CT Conclusions— In this prospective study of 700 aspirin-treated patients presenting for angiographic evaluation of coronary artery disease, residual platelet COX-1 function measured by serum thromboxane B 2 and COX-1-independent platelet function measured by PFA-100 collagen-ADP CT, but not indirect COX-1-dependent assays (arachidonic acid-stimulated platelet markers, shortened PFA-100 collagen-epinephrine CT), correlate with subsequent major adverse cardiovascular events. This study suggests that multiple mechanisms, including but not confined to inadequate inhibition of COX-1, are responsible for poor clinical outcomes in aspirin-treated patients, and therefore the term aspirin resistance is inappropriate. |
| Databáze: | OpenAIRE |
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