A New Cyclooxygenase‐2 Inhibitor, Rofecoxib (VIOXX®), Did Not Alter the Antiplatelet Effects of Low‐Dose Aspirin in Healthy Volunteers

The present study examined whether rofecoxib (VIOXX®), a new specific inhibitor of cyclooxygenase‐2 (COX‐2), would interfere with the desired antiplatelet effects of aspirin. Thus, the effects of rofecoxib on inhibition of ex vivo serumgenerated thromboxane B2 (TXB2) and platelet aggregation by low doses (81 mg) of aspirin were examined in healthy volunteers. This was a double‐blind, randomized, placebo‐controlled, parallel study of two treatment groups (n = 12 per group) in which subjects received 50 mg of rofecoxib or placebo for 10 days in a blinded fashion. Subjects also received 81 mg aspirin once on each of days 4 through 10 in an open‐label fashion. Blood for measurement of serum TXB2 production and platelet aggregation studies was collected on day 1 (prior to rofecoxib/placebo), on day 4 (prior to aspirin), and on day 10 (before and 4 hours following the seventh dose of aspirin). Platelet‐derived serum TXB2 (COX‐1 assay) was measured in blood clotted for 1 hour at 37°C. Platelet aggregation was independently induced employing 1 mM arachidonic acid and 1 μg/mL collagen as agonists. Rofecoxib administered alone had no significant effect on serum TXB2 production or platelet aggregation (day 4). TXB2 production was inhibited 98.4% by aspirin coadministered with either rofecoxib or placebo (day 10). Similarly, platelet aggregation induced by arachidonic acid was inhibited 93.7% and 93.5% by aspirin coadministered with either rofecoxib or placebo, respectively (day 10). The comparable values for inhibition of collagen‐induced platelet aggregation were 86.8% and 90.8%, respectively. No important clinical or laboratory adverse experiences were observed. In conclusion, rofecoxib alone (50 mg QD for 4 days) did not inhibit serum TXB2 production or platelet aggregation. In addition, rofecoxib (50 mg QD for 10 days) did not alter the antiplatelet effects of low‐dose aspirin (inhibition of platelet aggregation and TXB2 production). Rofecoxib was generally well tolerated when administered alone or in combination with low‐dose aspirin.