Optical platelet aggregation versus thromboxane metabolites in healthy individuals and patients with stable coronary artery disease after low-dose aspirin administration.
BACKGROUND
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 B2 (S-TxB2), urinary 11-dehydro-TxB2 (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-TxB2 >99% in healthy individuals (median 1.1 ng/mL, interquartile range (IQR) = 0.8;1.9 after aspirin) and in patients, S-TxB2 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 TxA2 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-TxB2 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-TxB2, 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.
Hedegaard
Sofie S
SS
Department of Cardiology, Aarhus University Hospital Skejby, Denmark.
Hvas
Anne-Mette
AM
Grove
Erik L
EL
Refsgaard
Jens
J
Rocca
Bianca
B
Daví
Giovanni
G
Kristensen
Steen D
SD
D000328:Adult; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003324:Coronary Artery Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology*; D013608:Tablets, Enteric-Coated; D013931:Thromboxanes / Q000097:blood / Q000378:metabolism* / Q000652:urine; D013997:Time Factors
D010975:Platelet Aggregation Inhibitors; D013608:Tablets, Enteric-Coated; D013931:Thromboxanes; D001241:Aspirin