A randomized, controlled study on the influence of acetaminophen, diclofenac, or naproxen on aspirin-induced inhibition of platelet aggregation

Nonsteroidal anti-inflammatory drugs (NSAID) may interfere with aspirin (acetylsalicylic acid) and increase the risk for cardiovascular events. The clinical relevance is uncertain. The aim of this study was to analyse the influence of a co-administration of aspirin and NSAID on platelet aggregation. In a randomized, placebo controlled trial, eleven healthy volunteers were studied during 4 separate study periods of 4 days each. Individuals were treated on each occasion with 100 mg aspirin daily in combination with either 3 × 1 g acetaminophen, 3 × 50 mg diclofenac, 3 × 250 mg naproxen, or 3 × 1 placebo. Primary hemostasis was assessed with a platelet function analyser (PFA-100®), which measures the closure time (CT) of a collagen- and epinephrine-coated pore by aggregating platelets in flowing blood. Naproxen enhanced the anti-aggregatory action of aspirin after 24 h (CT rising from 104 ± 16 s at baseline to 212 ± 69 s at 24 h, P < 0.001), which was not seen with any other drug combination. Diclofenac reduced the anti-aggregatory action of aspirin in the first two days, since the CT did not rise significantly (109 ± 19 s, 148 ± 56 s, and 168 ± 66 s at 0 h, 24 h, 48 h, respectively, P > 0.05). Acetaminophen had no effect compared with placebo. After 4 days of treatment platelet aggregation was similarly inhibited by all combinations. We conclude that a co-administration of NSAID and aspirin may interfere with platelet inhibition at the beginning of a treatment with an increase of naproxen and a decrease of diclofenac. This effect is lost after 4 days, suggesting that a regular daily co-administration of NSAID does not have an influence on platelet inhibition by aspirin.