Effects of Non-Steroidal Anti-Inflammatory Drugs and COX-2 Inhibitors on Aspirin-Induced Platelet Inhibition.
Authors: Sun Carol , Bergeron Angela , Wood Jennifer , Schweinle Jo Ellen , Lanza Frank L. , Cryer Byron , Dong Jin-Fei 
Published: April 2020

Abstract
Low dose aspirin has been widely used as a cardiac protective drug. It acts by inhibiting platelet activation and aggregation through the cyclooxygenase-1 pathway. However, such effects may be affected by short-term use of other drugs such as non-steroidal anti-inflammatory drugs (NSAIDs). We have conducted a multiple-dose, single-blind, parallel-group study to investigate the effects of over-the-counter NSAIDs and COX-2 inhibitors on arachidonic-induced platelet aggregation and thromboxane B2 (TxB2) production. We recruited 87 healthy individuals of 40-75 years of age, who met the inclusion and exclusion criteria by pretest screening. All subjects received 81 mg of aspirin (non-enteric coated and chewable) daily for eight days. Two hours after the 81 mg aspirin dose, the subjects received one of following drugs: acetaminophen (4 doses of 1000 mg daily), ibuprofen (3 doses of 400 mg daily), naproxen sodium (440 mg morning and 220 mg evening), a higher dose of aspirin (4 doses of 650 mg daily), celecoxib (2 doses of 200 mg daily) and rofecoxib (1 dose of 25 mg daily). Control individuals received only 81 mg of aspirin. Citrated blood was obtained before the treatment and at 2, 6, 12, and 24 hr during the first day and an identical schedule after 7 days of dosing (Day 8 of treatment). Platelet function was measured by arachidonic acid-induced platelet aggregation and serum levels of TxB2. We found that the maximal inhibitory effect (more than 85% reduction in aggregation) of 81 mg aspirin was reached more than 24 hr after initial drug intake; whereas it was observed within 6 hr in subjects receiving randomized 2600 mg of aspirin (but only took 1300 mg at time of blood draw). Similar to the higher dose of aspirin, both ibuprofen and naproxen sodium also significantly accelerated the inhibitory effects of low dose aspirin on platelet aggregation (Paired Student t test, p &lt; 0.01). In comparison, acetaminophen and two COX-2 inhibitors showed no additive effects with 81 mg of aspirin. Consistent with aggregation studies, the inhibition of TxB2 production was significantly greater than those with 81 mg of aspirin only at 6, 12, and 24 hr after initial drug intake for 2600 mg of aspirin, ibuprofen, and naproxen, but not for acetaminophen, celecoxib, and rofecoxib. Contrary to a report by Catella-Lawson et al, we found that ibuprofen did not interfere, but rather slightly enhanced, aspirin-induced inhibition of platelet aggregation. The reason for the discrepancy remains unknown, but may be attributed to the type of aspirin used (enteric-coated vs. non-enteric-coated) and different schedules of drug intakes between the two studies. Finally, it may also be due to the fact that our subjects were in their normal environments and not in a clinical research unit. In conclusion, we found that acetaminophen and COX-2 inhibitors did not affect the course of the low-dose aspirin action on platelets. Although ibuprofen and naproxen have had no additive effects, they accelerated the action of 81 mg of aspirin on platelet aggregation.