Influence of non-steroidal anti-inflammatory drugs on antiplatelet effect of aspirin

Abstract

What is known and Objective: It has been reported that ibuprofen interferes with the antiplatelet effect of low-dose aspirin. This interaction is ascribed to steric hindrance at the active site of cyclooxygenase-1 by ibuprofen, when aspirin is administered after ibuprofen. However, whether other nonsteroidal anti-inflammatory drugs (NSAIDs) interact with aspirin similarly is not well defined. The aim of this study was to assess the influence of nine NSAIDs on the antiplatelet effect of aspirin. Methods: We investigated the antiplatelet effect of NSAIDs using steady-state plasma concentration reported after usual doses. We studied the in vitro antiplatelet effect of NSAID alone, aspirin alone, aspirin before NSAID addition and aspirin after NSAID addition to platelet-rich plasma. The rates of platelet aggregation induced by collagen were determined. The final concentration of aspirin used was the 50% effective concentration (EC 50 ) previously estimated in vitro. Results and Discussion: Ibuprofen and mefenamic acid interfere with the antiplatelet effect of aspirin when added before the latter. The rate of platelet aggregation was reduced by 48AE1% and 22AE7%, respectively. The other NSAIDs tested did not significantly affect the aspirin antiplatelet effect when exposure was prior to aspirin. None of the nine NSAIDs altered the aspirin effect if administration followed that of aspirin. What is new and Conclusion: Naproxen and flurbiprofen have significant antiplatelet effects at plasma concentrations seen with usual doses. Our in vitro model suggests that the antiplatelet effect of aspirin is significantly diminished when taken after, but not before, ibuprofen or mefenamic acid. None of the other NSAIDs tested had any effect irrespective of the timing of dosing.

Evaluation of Toxicological Profile of Ibuprofen in Wistar Albino Rats

“…This observation is consistent with the result of a similar study on aquatic animals [30]. Although, NSAIDs are known to have antiplatelet activities [10], the antiplatelet effects of ibuprofen in relation to dose and duration of exposure is not fully established. Our observation of the reduction of platelet counts after 14 and 28 days of ibuprofen exposure, and a non-effect after 7 days of exposure in this study, strongly suggests that the antiplatelet effect of ibuprofen is more important with duration of exposure than dose.…”

“…However, most of such reports are on high dose levels of the agents (> clinical doses) and existing data on ibuprofen-mediated renal toxicity in relation to duration of exposure is not exhaustive. Furthermore, NSAIDs are known to have antiplatelet activities [10], however, the antiplatelet effects of ibuprofen in relation to dose and duration of exposure is not fully established. Importantly, ibuprofen is an over-the-counter NSAID, with the consequence of an increase in its usage and toxicological potentials.…”

Topical diclofenac does not affect the antiplatelet properties of aspirin as compared to the intermediate effects of oral diclofenac: A prospective, randomized, complete crossover study

“…Similarly to the previous in vitro studies, this study found that both flurbiprofen and naproxen caused substantial inhibition on aspirin's antiplatelet effects, whereas other NSAIDs, such as diclofenac, had insignificant effects on aspirin's antiplatelet activity regardless of administration time. 13 These studies are in vitro in nature and do not establish whether this interaction exists in vivo.…”

Updates on NSAIDs in patients with and without coronary artery disease: pitfalls, interactions and cardiovascular outcomes

“…Ibuprofen and naproxen, but not etoricoxib or meloxicam, taken 2 h before aspirin, significantly inhibited the aspirin effect. In another study, Yokoyama et al tested nine NSAIDs (loxoprofen, ibuprofen, diclofenac, naproxen, mefenamic acid, flurbiprofen, indomethacin, etodolac and meloxicam) [18]. They concluded that ibuprofen and mefenamic acid reduced platelet aggregation when given before aspirin.…”