Parecoxib sodium does not impair platelet function in healthy elderly and non-elderly individuals - Two randomised, controlled trials

Objective: To compare the effects of parecoxib sodium, an injectable prodru g of a cyclo-oxygenase-2-specific inhibitor, and ketorolac on platelet func tion and bleeding time in elderly individuals and non-elderly adults. Design and Setting: Double-blind, randomised, active- and placebo-controlle d, parallel-group studies. Patients and Participants: Healthy men and women, between the ages of 65 an d 95 years (62 elderly individuals) or 18 and 55 years (48 non-elderly indi viduals). Methods: Participants received placebo or active medication: parecoxib sodi um 40 mg twice daily intravenously for 8 days (both studies), ketorolac 15 mg four times daily intravenously for 5 days (elderly individuals) or 30 mg four times daily intravenously for 5 days (non-elderly individuals). Ex vi vo platelet aggregation responses to arachidonate, collagen and adenosine d iphosphate (ADP), bleeding time and serum thromboxane B-2 (TxB(2)) levels w ere measured. Results: In both studies, parecoxib sodium had little or no effect on arach idonate-induced platelet aggregation, whereas ketorolac caused statisticall y significant and sustained decreases in platelet aggregation throughout th e entire drug administration period. Parecoxib sodium also had little or no effect on collagen- or ADP-induced aggregation compared with ketorolac. Al though there was a high degree of variability in bleeding times, significan t prolongation of bleeding times was observed only in the ketorolac groups in both studies. Parecoxib sodium had no effect on serum TxB2 concentration s in non-elderly individuals. In elderly individuals, ketorolac significant ly and profoundly reduced TxB2 levels at all assessments, whereas parecoxib sodium showed less of a reduction. Conclusion: Although a direct correlation has not been proven, patients wit h reduced platelet function do appear to be at a higher risk of experiencin g increased bleeding during surgery. Thus, the absence of effect on platele t aggregation and bleeding time observed in these studies suggests that par ecoxib sodium is less likely to be associated with excessive bleeding durin g surgery, and therefore is potentially safer than ketorolac for use in pat ients undergoing surgery, irrespective of age.