Some studies found that concomitant use of conventional NSAIDs, such as naproxen and ibuprofen, with low-dose aspirin impeded the antiplatelet effects of aspirin, though this effect was not seen with selective COX-2 inhibitors. The majority of studies showed that ibuprofen interfered with the antiplatelet effects of aspirin. Evidence surrounding naproxen, which is often used in patients with known cardiovascular risk, was highly variable, with some studies reporting evidence supporting an interaction and others showing the opposite.

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John Horn, PharmD, of the department of pharmacy at the University of Washington in Seattle, told Hematology Advisor, “Besides the potential for NSAIDs to inhibit the antiplatelet effects of aspirin, the combination is also associated with an increased risk of bleeding, particularly gastrointestinal bleeds.”

“Acetaminophen would be an appropriate [alternative] as it does not alter platelet function,” he continued. “It would avoid both the risk of reduced cardioprotection from the aspirin and the increased risk of bleeding resulting from the combination of aspirin and NSAID.”

Current literature has suggested that modifying timing of administration may also help manage this drug interaction. For instance, taking naproxen no less than 2 hours following aspirin administration can lessen the interaction, as can single or twice daily dosing of naproxen.

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Clinical Significance and Moving Forward

The clinical importance of this drug interaction has not been studied in randomized, adequately controlled clinical trials. Conducting such trials would be challenging for several reasons, including the presence of confounding variables such as patient comorbidities.

“If my patients are [on] aspirin for secondary prevention, I generally tell them to avoid taking over-the-counter NSAIDs at the same time, unless specifically requested by their health care provider,” stated Dr Michos. “I warn them about the potential for interaction, [which could lead to] both reduced efficacy of aspirin and [the] potential for increased bleeding.”

“If [an] NSAID has to be given because there are no suitable alternatives, I would recommend giving [the] NSAID at least 2 hours after taking the aspirin dose,” Dr Michos concluded.


1. Gurbel P, Tantry U, Weisman S. A narrative review of the cardiovascular risks associated with concomitant aspirin and NSAID use [published online November 7, 2018]. J Thromb Thrombolysis. doi: 10.1007/s11239-018-1764-5.