Optical platelet aggregation versus thromboxane metabolites in healthy individuals and patients with stable coronary artery disease after low-dose aspirin administration

Introduction: Aspirin reduces cardiovascular events in patients with coronary artery disease (CAD), but studies report a highly variable response to aspirin, often referred to as 'aspirin low-responsiveness'. We investigated whether 75 mg of daily non-enteric coated aspirin would completely inhibit the platelet cyclooxygenase-1 activity to a comparable extent in healthy individuals and stable CAD patients. Methods: We assessed serum thromboxane B-2 (S-TxB(2)), urinary 11-dehydro-TxB(2) (U-TxM) and arachidonic acid-induced optical platelet aggregometry (OPA) in 44 CAD patients on aspirin and in 22 healthy individuals before and after aspirin. OPA was performed in duplicate for four consecutive days during aspirin treatment after one week of treatment. Compliance was optimized by face-to-face interviews and pill counting and confirmed by S-TxB(2) measurements. Results: Aspirin inhibited S-TxB(2) > 99% in healthy individuals (median 1.1 ng/mL, interquartile range (IQR) = 0.8; 1.9 after aspirin) and in patients, S-TxB(2) Was reduced to a similar level (0.9 ng/mL (0.7; 1.5)). Healthy individuals had a median U-TxM of 278.5 pg/mg creatinine (229.5; 380.0) before aspirin and 68.5 pg/mg creatinine (59.0; 99.7) on aspirin corresponding to an average 74% inhibition of the endogenous TxA(2) biosynthesis. In patients median U-TxM was 67.5 pg/mg creatinine (54.0; 85.5). Seven study participants (11%) were aspirin low-responders according to OPA, but none had S-TxB(2) in the highest quartile. Conclusions: Low-dose aspirin suppressed S-TxB(2) to comparable levels in CAD patients and healthy individuals. Despite an almost complete inhibition of S-TxB(2), some participants were low-responders according to OPA. Thorough compliance control and use of thromboxane-specific assays are important when measuring platelet response to aspirin. (C) 2009 Elsevier Ltd. All rights reserved.