Public Release: 

Aspirin resistance increases risk of death

American Heart Association

DALLAS, March 26 - For the first time, researchers have shown that people who are aspirin resistant have a higher risk of dying from heart disease than people who are not aspirin resistant, according to a study in today's rapid access issue of Circulation: Journal of the American Heart Association.

Aspirin blocks the formation of thromboxane A2, a chemical in the body that makes platelets sticky and promotes blood clotting. However, lead author John W. Eikelboom, MBBS, says it appears that aspirin does not effectively block thromboxane synthesis in some people. This makes them resistant to the protective effects of the drug.

In the study, patients taking aspirin who had a high level of thromboxane in their urine had a 3.5 times higher risk of cardiovascular death than patients who had the lowest level says Eikelboom, a clinical lecturer at the University of Western Australia, Royal Perth Hospital, Perth, Australia.

The American Heart Association recommends aspirin for all patients with artery disease and a second antiplatelet medicine for those with uncontrolled chest pain called unstable angina.

Eikelboom cautions that the findings don't suggest a need to limit aspirin use. For most patients, aspirin therapy can reduce the risk for cardiovascular events by 25 percent. "Our results suggest that some patients may need more protection than aspirin alone can offer," he says.

Researchers used data collected by the Heart Outcomes Prevention Evaluation (HOPE) study. This was a randomized, placebo-controlled study that compared the efficacy of a blood pressure drug, ramipril, and vitamin E to prevent heart attacks or stroke in patients with heart disease. The current study is based on data collected on 5,529 patients enrolled at 129 Canadian study sites. All patients provided baseline urine specimens, which were analyzed for levels of a chemical called 11-dehydro thromboxane B2, a byproduct of thromboxane A2.

High levels of 11-dehydro thromboxane B2 in urine can identify patients who are resistant to aspirin. These people may benefit from alternative antiplatelet therapies or treatments that more effectively block thromboxane production.

The researchers identified patients who were taking aspirin for at least six months before study entry and kept taking aspirin throughout the study. During a five-year follow-up, 488 of these patients had a heart attack, stroke or fatal event. Another 488 aspirin-therapy patients who were age and gender matched and did not have an event during follow-up were used as controls. Patients were free to select aspirin doses ranging from 80mg to 325mg a day.

When the researchers divided the cases and controls into quartiles based on 11-dehydro thromboxane B2 levels, those in the highest quartile had twice the risk for heart attack as those in the lowest quartile.

The risk for any cardiovascular event was 1.8 times higher for those in the highest quartile compared to those in the lowest quartile. "The increased risk was consistent. Those in the third quartile had a higher risk than those in the second quartile, while the second was higher than the first," Eikelboom says. Moreover, the increased risk was independent of other risk factors such as high blood pressure, high cholesterol, obesity, diabetes and smoking.

The researchers didn't find an association between 11-dehydro thromboxane B2 levels and stroke, but Eikelboom says this is probably due to the small number of stroke cases.


Co-authors are: Jack Hirsh, M.D.; Jeffrey I. Weitz, M.D.; Marilyn Johnston, ART; Qilong Yi, Ph.D.; and Salim Yusuf, D.Phil.

NR02 - 1040 (Circ/Eikelboom)

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