Interference of NSAIDs with the thrombocyte inhibitory effect of aspirin: a placebo-controlled, ex vivo, serial placebo-controlled serial crossover study.
OBJECTIVE
Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA) are often prescribed concurrently in patients with nociceptive pain and cardiovascular comorbidity. NSAIDs and ASA inhibit the same COX-enzymes, and thus may interact. ASA's cardioprotective antiplatelet effect is entirely COX-1 dependent. NSAIDs can be either non-COX-1 and COX-2 selective or COX-2 selective. The aim of this study was to examine the interaction between ASA and different selective and nonselective NSAIDs on thrombocyte function.


METHODS
Single-blind, prospective, placebo-controlled, ex vivo, serial crossover trial of 3-day cycles separated by washout periods of at least 12 days in 30 healthy volunteers, evaluating interaction on ASA's antithrombocyte effect by naproxen, ibuprofen, meloxicam, or etoricoxib taken 2 h before ASA. Ex vivo thrombocyte function, closure time (CT) in seconds, was measured using the Platelet Function Analyzer 100 (PFA-100). CT prolongation during a cycle reflects thrombocyte inhibitory effect. ASA nonresponse was defined as CT prolongation <40 % in the placebo cycle. ASA nonresponders were excluded. Wilcoxon signed-rank was used to evaluate NSAID effect on ASA-induced CT prolongation.


RESULTS
Ibuprofen and naproxen inhibit ASA's antithrombocyte effect below the nonresponse threshold. Etoricoxib and meloxicam do not cause relevant change in ASA thrombocyte inhibition. Naproxen has an inherent weak thrombocyte inhibitory action below the ASA response threshold.


CONCLUSIONS
COX-1 affinity determines the interaction between NSAIDs and ASA on thrombocyte adhesion and aggregation. Ibuprofen and naproxen, but not etoricoxib or meloxicam, taken 2 h before ASA, significantly inhibit ASA's antithrombocyte effect.
Arthritis Center Twente, University Twente and Medisch Spectrum Twente, 7500KA Enschede, Netherlands. i.meek@reuma.umcn.nl
I L
IL
Meek
H E
HE
Vonkeman
J
J
Kasemier
K L L
KL
Movig
M A F J
MA
van de Laar
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D001241:Aspirin / Q000008:administration & dosage*; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D018592:Cross-Over Studies; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D000077613:Etoricoxib; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects; D008297:Male; D000077239:Meloxicam; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects; D009426:Netherlands; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010979:Platelet Function Tests; D011446:Prospective Studies; D011725:Pyridines / Q000009:adverse effects; D018570:Risk Assessment; D013450:Sulfones / Q000009:adverse effects; D013843:Thiazines / Q000009:adverse effects; D013844:Thiazoles / Q000009:adverse effects; D013997:Time Factors; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D013450:Sulfones; D013843:Thiazines; D013844:Thiazoles; D009288:Naproxen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D001241:Aspirin; D000077239:Meloxicam; D007052:Ibuprofen; D000077613:Etoricoxib