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Clinical Articles, Lead Article

Aspirin resistance “very rare”

True pharmacological resistance to aspirin is rare, according to a study1 which failed to identify a single case of true drug resistance, published recently in Circulation.

Researchers aimed to determine the commonality of a mechanistically consistent, stable and specific phenotype of true pharmacological resistance to aspirin – such as might be explained by genetic causes.

400 healthy volunteers were screened for their response to a single oral dose of 325 mg immediate release or enteric coated aspirin. Response parameters reflected the activity of aspirin’s molecular target, cyclooxygenase (COX)-1. Individuals who appeared “aspirin resistant” on one occasion underwent repeat testing, and if still “resistant” were exposed to low dose enteric coated aspirin (81 mg) and clopidogrel (75 mg) for one week each.

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.

The authors conclude that pseudoresistance, reflecting delayed and reduced drug absorption, complicates enteric coated but not immediate release aspirin administration.

Study author, Dr Tilo Grosser

Study author, Dr Tilo Grosser

Author, Dr Tilo Grosser (University of Pennsylvania, Philadelphia, USA) spoke to BJC Arrhythmia Watch on the study’s main observations: “Most people respond perfectly fine to aspirin, if one monitors carefully the pharmacological effects the drug has on its molecular target in platelets…true pharmacological resistance to aspirin, as might be caused by genetic variation, is very rare”.

“It is easy to make a false diagnosis of aspirin resistance when people take enteric coated aspirin. This formulation is very popular because many believe it is less gastrotoxic then plain aspirin. While this claim has never been proven in clinical outcome trials, coating delays and reduces aspirin absorption substantially”.

“In our study, we would have called roughly 30% of the volunteers who took the coated formulation ‘aspirin resistant,’ had we looked only at a single time point. Coated aspirin did eventually have the full effect, but it had to be taken every day for a few days.”

“It is also easy to make a false diagnosis of aspirin resistance by using assays that do not specifically test aspirin’s target enzyme, COX-1, in platelets. For example, we found that a US Food and Drug Administration (FDA) approved laboratory test which measures urinary thromboxane was unable to separate people who responded well to plain aspirin from those who had the delayed response to coated aspirin. The reason is probably that thromboxane is not specifically produced by platelets; there are many tissues that contribute to its formation and the urine test picks them all up”.

He continued by listing the study’s main implications for patient care:

“Testing for aspirin resistance is rightly not recommended by most professional societies. Situations where patients may not respond appropriately to low aspirin should not be confused with drug resistance”.

“There is really no reason why patients should be prescribed coated aspirin, which has never shown a reduction of stomach bleeds in clinical trials. Coating does render the absorption of aspirin much more variable, and may increase the chance of a false diagnosis of aspirin resistance. A false diagnosis of aspirin resistance may lead to an unnecessary increase in the aspirin dose, or the prescription of another much more expensive anti-platelet drug,” he concluded.


1. Grosser T, Fries S, Lawson JA, Kapoor SC, Grant GR, FitzGerald GA. Drug resistance and pseudoresistance: an unintended consequence of enteric coating aspirin. Circulation 2012.​CIRCULATIONAHA.112.117283

Published on: December 20, 2012

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