The study's blood-based test of gene activity revealed a level of resistance to aspirin because of a genetic effect on the cardiovascular system.
The research adds to the potential for a future test to see who will benefit from aspirin and who will not. The research also gives clues about individual people's risk of getting a heart attack.
Aspirin has been widely used as medication for heart disease and stroke patients for the last 50 years, used for its blood-thinning capabilities. However, doctors have been unclear about how aspirin works and why it doesn't help all heart patients.
Researchers at Duke University Medical Center analyzed two groups of heathy volunteers and one group suffering from heart disease. The heart disease patients were given a low dosage of aspirin as a part of their treatment. The healthy volunteers were prescribed a 325mg dosage of aspirin each day for up to one month.
The researchers then looked at the impact of aspirin on the function of gene expression and the function of platelets, the blood cells responsible for clotting.
Following the administration of the aspirin, the gene profiling revealed a genetic 'aspirin response signature'. This matched an insufficient platelet response to aspirin therapy in both the heart disease patients and healthy patients.
Geoffrey Ginsburg, director of genomic medicine at Duke's Institute for Genome Sciences and Policy, said:
"We give the same dose to all patients, but maybe some patients need a larger dose of aspirin, or maybe they need a different therapy entirely.
"We need better tools to monitor patients and adjust their care accordingly, and the findings from our study move us in that direction."
This isn't the first study to measure the level of aspirin resistance. A recent study from Circulation, the journal of the American Heart Association, conducted a platelet test on 400 healthy volunteers. It was found that around one-third of the volunteers were resistant to the effects of aspirin in everyday use.
As well as measuring the effectiveness of aspirin, the researchers of this most recent study say the genetic response signature can also act as a predictor of patients who are at risk of a heart attack.
Deepak Voora, assistant professor of medicine at Duke and lead author of the study explained: "There is something about the biology of platelets that determines how well we respond to aspirin and we can now capture that with a genomic signature in blood."
Rochelle Long of the US National Institute of General Medical Sciences said: "Nearly 60 million people take aspirin regularly to reduce their chances of heart attack and death, but it doesn't work for everyone. This work may eventually lead to a simple blood test to identify those who do not benefit form aspirin, enabling them to seek other therapeutic options."