MEDIA STATEMENT
26th February 2008

Possible effects of ibuprofen on platelet inhibition by aspirin

A US study published in the Journal of Clinical Pharmacology (2008;48:117-22) has suggested that ibuprofen interferes with the antiplatelet effects of low-dose aspirin with clinically significant consequences. This is one of several studies that have investigated the clinical importance of this interaction and their conclusions have been contradictory.

The new study
This study was in two parts. First, 10 healthy volunteers took (on three occasions) a single dose of aspirin 325 mg, ibuprofen 400 mg or ibuprofen followed after 2 hours by aspirin. When given alone, aspirin inhibited platelet function by 76 - 91 per cent (depending on how it was measured) after 2 hours; normal platelet function was restored after 72 - 96 hours. Ibuprofen alone inhibited platelet function by 33 - 45 per cent, with a return to normal function after 4 - 6 hours. When aspirin was taken after ibuprofen, the effect on platelet function was similar to that with ibuprofen alone.

In the second part, 28 patients taking low-dose aspirin together with ibuprofen or naproxen were found to have no significant inhibition of platelet function. Eighteen agreed to stop taking their NSAID and continue aspirin alone; platelet function was then significantly inhibited.

Prescribing advice
The new study is the latest of several to investigate the interaction between ibuprofen and aspirin, either in a laboratory setting or by comparing clinical endpoints in patients taking aspirin alone with those in patients taking aspirin and ibuprofen together. While there is a consensus that an interaction does occur in the laboratory, their findings about whether this matters to patients and health professionals have been contradictory.

In 2005, the European regulatory authorities reviewed the cardiovascular safety of NSAIDs. In 2006, the European Medicines Agency stated:(1)

'Ibuprofen has been shown to interact with aspirin ex vivo, reducing its inhibition of Cox-1. However, observational studies and clinical trials have shown inconclusive results regarding the effect of combination of NSAIDs and aspirin therapy on mortality risk and incidence of myocardial infarction, and no firm conclusions are possible.'

More specifically, the UK Committee on Safety of Medicines addressed the possibility that ibuprofen may reduce the effectiveness of low-dose aspirin. It stated:(2)

'Although platelet aggregation studies have demonstrated an interaction
between aspirin and ibuprofen, a clinically important effect has not been
clearly demonstrated in epidemiological studies or clinical trials.'

In November 2007 the UK National Prescribing Centre (NPC) commented:(3)

'Although there is ex-vivo evidence of an interaction between aspirin and ibuprofen, there is inadequate clinical evidence to suggest that there is a loss in the cardioprotective effect of aspirin when given together.'

The NPC adds: in the US, the Food and Drug Administration has advised that the doses of ibuprofen and aspirin should be staggered to minimise any interaction (e.g., ibuprofen at least 30 minutes after and 8 hours before aspirin). The UK Medicines Health Regulatory Agency and other European Union regulators keep this issue under review but no updated prescribing advice has been issued in Europe in view of the lack of supportive clinical evidence.

Summary
The new study adds to the body of knowledge about the interaction between low-dose aspirin and ibuprofen but does not provide a definitive answer to the question of whether the effects are clinically significant especially in short-term OTC use of ibuprofen . European regulatory authorities have concluded that the significance of such an interaction is unclear and the evidence is insufficient to show that it is clinically important.

References

1. European Medicines Agency. Public CHMP assessment report for medicinal products containing non-selective non steroidal anti-inflammatory drugs (NSAIDs). EMEA/CHMP/442130/2006. November 2006 (www.emea.europa.eu/pdfs/human/opiniongen/44213006en.pdf; accessed 6/2/08)

2. Committee on Safety of Medicines. Cardiovascular Safety of Non-Steroidal Anti-inflammatory Drugs. Overview of key data. August 2005 (www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dDocName=con1004304&RevisionSelectionMethod=Latest; accessed 6/2/08)

3. National Prescribing Centre. Cardiovascular and gastrointestinal safety of NSAIDs. MeReC Extra Issue No. 30. November 2007 (http://www.npc.co.uk/MeReC_Extra/2008/pdfs/MeReC_Extra_No30.pdf; accessed 6/2/08)

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