Effects of aspirin and clopidogrel in healthy men measured by platelet aggregation and PFA-100.
There are no generally accepted definitions for low-response (frequently called resistance) to the platelet inhibitors, aspirin and clopidogrel. Low-response may increase the risk of cardiovascular events in atherosclerotic patients. We aimed to define the normal drug responses in healthy men. Platelet function was measured in 20 healthy men during 11 days of aspirin or clopidogrel intake, using light transmission aggregometry (LTA) and the Platelet Function Analyzer 100 (PFA-100). The lower limits for LTA at baseline were 64% and 61%, using arachidonic acid and ADP as agonists, respectively. During aspirin intake the LTA results were stable from day to day, and an upper limit of 9% arachidonic acid stimulated aggregation was found. Clopidogrel intake was best shown by ADP induced aggregation. However, two out of 20 individuals exhibited low-response to clopidogrel. In the remaining 18 volunteers an upper limit of 48% aggregation was found. We found an upper limit for collagen-epinephrine stimulated PFA-100 results of 166 s at baseline. During aspirin intake, these results varied considerably from day to day in nine out of 20 men, resulting in an overlap between the reference ranges at baseline and during therapy. In conclusion, platelet inhibition by aspirin and clopidogrel assessed by aggregometry was stable during 11 days of treatment and reference ranges were established. The PFA-100 results varied greatly and low-response was not precisely defined by this method.
Madsen
Esben H
EH
Department of Clinical Biochemistry, Centre for Cardiovascular Research, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. ehm@rn.dk
Schmidt
Erik B
EB
Maurer-Spurej
Elisabeth
E
Kristensen
Søren R
SR
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D000077144:Clopidogrel; D003094:Collagen / Q000494:pharmacology; D018592:Cross-Over Studies; D051545:Cyclooxygenase 1 / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009391:Nephelometry and Turbidimetry / Q000295:instrumentation; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010979:Platelet Function Tests / Q000295:instrumentation; D012016:Reference Values; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D003094:Collagen; D000077144:Clopidogrel; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D013988:Ticlopidine; D001241:Aspirin; D004837:Epinephrine