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Updated 16 February 2013

True aspirin resistance extremely rare

Pharmacological resistance to low-dose aspirin is extremely rare, say researchers from the University of Pennsylvania in Philadelphia.


Pharmacological resistance to low-dose aspirin is extremely rare, say researchers from the University of Pennsylvania in Philadelphia.

Among 400 healthy volunteers given a single oral dose of 325 mg regular "immediate release" or enteric coated aspirin, they couldn't find a single case of true aspirin resistance.

They did find "pseudoresistance" due to delayed and reduced absorption caused by the enteric coating found on most brands of aspirin, however.

"The message to clinicians is that true resistance is vanishingly rare, so don't waste time and money on screening patients prior to putting them on aspirin, either using point of care platelet tests or urine tests for thromboxane metabolites," Dr Garret A. FitzGerald, director of UPenn's Institute of Translational Medicine and Therapeutics (ITMAT), who worked on the study, told Reuters Health.

"Secondly, there is no rational basis for selecting coated aspirin over immediate release (uncoated) aspirin which is cheaper; it hasn't been shown to protect the stomach and may lead to a false call of aspirin resistance," he said.

How the study was done

In a report online today in Circulation, the study team says estimates of the frequency of aspirin resistance have varied from 5% to 20% in most studies.

The UPenn researchers say they designed their study to determine the "true commonality of a mechanistically consistent, stable and specific phenotype of true pharmacological resistance to aspirin, such as might be explained by genetic causes."

They measured platelet aggregation induced by arachidonic acid, serum thromboxane formation and urinary excretion of a thromboxane metabolite - all reflecting the activity of aspirin's molecular target (COX-1) - before and after a single 325 mg dose of regular aspirin and enteric coated aspirin.

Individuals who appeared to be "aspirin resistant" underwent repeat testing; those who failed to respond to aspirin twice were exposed to low-dose enteric coated aspirin (81 mg) and clopidogrel (75 mg) for one week each in a crossover design.

The researchers report that "variable absorption caused a high frequency of apparent resistance to a single dose of 325 mg enteric coated aspirin (up to 49%) but not to immediate release aspirin (0%). All individuals responded to aspirin upon repeated exposure, extension of the post dosing interval or addition of aspirin to their platelets ex vivo."

Experts couldn’t  find a true case 

Thus, they say, they failed to find a single case of true aspirin resistance in this study of 400 healthy volunteers. "By contrast, pseudoresistance due to delayed and reduced drug absorption was common after ingestion of enteric coated aspirin."

"These observations question the value of seeking to diagnose aspirin resistance with single point-of-care diagnostic approaches and support the finding of inconsistent platelet inhibition following enteric coated preparations of aspirin," Dr FitzGerald and colleagues conclude.

"Aspirin resistance has been overblown," added Dr Joel S. Bennett, professor of medicine at University of Pennsylvania who was not involved in the study.

"I think the study is reassuring," he told Reuters Health, "in the sense that if one knows that a patient is compliant with taking aspirin, the chances that the aspirin is not working are very, very low. But physicians need to be aware of aspirin's limitations (despite the Bayer ads on TV, it is not the cure for MI and stroke), but it clearly has a place and is effective in the prevention of arterial thrombosis.

 We need to continue to look for more effective agents or more effective combinations of drugs that can prevent these clots with excessive side effects like bleeding," Dr Bennett said.

 (Reuters Health, Megan Brooks, December 2012)

Read more: 

Daily aspirin risks outweigh gains

Eating vegetables may protect pancreas

Aspirin use not tied to breast cancer risk


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