Abstract
BackgroundLow-dose aspirin irreversibly inhibits platelet cyclooxygenase-1 (COX-1) and suppresses platelet aggregation. It is effective for secondary prevention of cardiovascular events. Because nonsteroidal anti-inflammatory drugs (NSAIDs) reversibly bind with COX-1, the antiplatelet effects of aspirin may be suppressed when NSAIDs are co-administered. This interaction could be avoided by avoiding simultaneous administration; however, the minimum interval that should separate the administration of aspirin and loxoprofen is not well known. In this study, we investigated how to avoid the influence of NSAIDs on the antiplatelet effects of aspirin. An in vitro experiment was performed to investigate the influence of ibuprofen and loxoprofen at various concentrations on aspirin’s antiplatelet action.MethodsPlatelet aggregation and thromboxane B2 (TXB2) levels were measured after addition of aspirin only and NSAIDs plus aspirin to platelet-rich plasma. NSAIDs were used at their maximum plasma concentrations, the assumed concentration after 6 h (for loxoprofen only), and the assumed concentration after 12 h of taking one clinical dose. Platelet aggregation threshold index (PATI), defined as the putative stimulus concentration giving 50% aggregation, was calculated as an index of aggregation activity.ResultsPATI decreased in ibuprofen plus aspirin group compared to that in the aspirin only group, regardless of ibuprofen concentration. Furthermore, PATI significantly decreased when aspirin was added after loxoprofen-trans-OH addition at the maximum concentration (4.1 ± 0.1 μg/mL), compared to that in aspirin only group (5.9 ± 0.1 μg/mL). PATI showed no significant difference after addition of loxoprofen at the assumed concentration after 6 h (aspirin only group, 5.0 ± 0.5 μg/mL; loxoprofen-trans-OH plus aspirin group, 4.9 ± 0.4 μg/mL).In addition, TXB2 concentration tended to decrease with increasing PATI.ConclusionsIt is desirable to avoid ibuprofen co-administration with the usual once-daily low-dose aspirin therapy; however, a 6-h interval between loxoprofen and aspirin could avoid this potential interaction when loxoprofen is taken before aspirin.
Highlights
Low-dose aspirin irreversibly inhibits platelet cyclooxygenase-1 (COX-1) and suppresses platelet aggregation
We previously reported that the antiplatelet effect of aspirin was inhibited by ibuprofen but not the other five nonsteroidal anti-inflammatory drugs (NSAIDs) investigated in an in vitro experimental study [15]
thromboxane B2 (TXB2) concentrations in platelet suspension of the control, aspirin only, and ibuprofen (Cmax) plus aspirin groups were 1400 ± 300, 200 ± 30, and 930 ± 290 ng/mL, respectively, which decreased with increasing Platelet aggregation threshold index (PATI) (Fig. 3a)
Summary
Low-dose aspirin irreversibly inhibits platelet cyclooxygenase-1 (COX-1) and suppresses platelet aggregation. It is effective for secondary prevention of cardiovascular events. Because nonsteroidal anti-inflammatory drugs (NSAIDs) reversibly bind with COX-1, the antiplatelet effects of aspirin may be suppressed when NSAIDs are co-administered. Low-dose aspirin is widely used for angina pectoris, myocardial infarction, ischemic cerebro-vascular disease, Kawasaki disease, and for prevention of thromboembolism after cardiac surgery. It inhibits cyclooxygenase-1 (COX-1) in the platelets, suppresses arachidonic acid metabolism, and prevents the synthesis of thromboxane A2 (TXA2), a compound that induces platelet aggregation [3]. When COX-1 in the platelets is acetylated by aspirin, the antiplatelet effects of aspirin are suggested to depend on platelet turnover and to be maintained until new platelets, unacetylated by aspirin, are produced [5]
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