The impact of selective and non-selective non-steroid anti-inflammatory drugs on secondary hemostasis in healthy volunteers.
BACKGROUND
Clinical and epidemiological studies have associated selective COX-2 inhibitors with an increased risk of cardiovascular events. There are no clinical studies on the possible effects of these drugs on secondary hemostasis. The hypothesis for this study is that the use of selective COX-2 inhibitors could affect the secondary hemostasis and by that increase the risk of cardiovascular events in a population at high risk.


METHODS
An open-label randomized cross-over study was performed in 20 healthy male volunteers. The study consisted of two periods of each 21 days with medication, either celecoxib 100 mg b.i.d. or naproxen 250 mg b.i.d. Treatment periods were separated by a washout period of 28 days. Blood samples were obtained before the first medication period, and at the end of each medication period. Primary effect parameter was FXII level. Secondary effect parameters included a wide range of coagulation factors involved in secondary hemostasis.


RESULTS
There was no statistically significant effect of celecoxib or naproxen on the primary effect parameter. Protein C activity was significantly decreased after treatment with naproxen (P<0.01), compared to baseline. Platelet function, demonstrated as closure time (CT), was at baseline 118+/-24 sec. (mean+/-SD). Naproxen prolonged CT to 171+/-50 sec. (P<0.001). Celecoxib did not change CT significantly (119+/-24 sec.).


CONCLUSIONS
Neither the selective COX-2 inhibitor celecoxib, nor the non-selective NSAID naproxen caused any change in the primary effect parameter from the secondary hemostasis.
Schjerning
Ole
O
Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, 5000 Odense C, Denmark. ole@schjerning-mail.dk
Larsen
Torben B
TB
Damkier
Per
P
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000068579:Celecoxib; D018592:Cross-Over Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005174:Factor XII / Q000378:metabolism*; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D009288:Naproxen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D009288:Naproxen; D005174:Factor XII; D000068579:Celecoxib