Aspirin resistance: Fact or fable?

Coronary heart disease is the single leading cause of death in the Western world. Aspirin is a fundamental part of the prevention and treatment of coronary heart disease and is used by millions of patients worldwide.

Most coronary heart disease deaths are caused by platelets sticking together and forming blood clots (thrombosis) that block blood flow within heart arteries and result in heart attacks. By inhibiting thrombosis, aspirin keeps platelets from sticking together by specifically blocking an important enzyme, COX-1, within the platelet.

Recent studies suggest that there may be a small group of patients who are resistant to the effects of aspirin. The definition of aspirin resistance is the failure of aspirin to block its intended target, COX-1. These latest findings demonstrate that aspirin resistance is rare at all doses (81-325mg daily doses) in patients with coronary artery disease when it is measured by methods that specifically indicate the level of COX-1 inhibition.

One hundred and ten patients with a history of coronary artery disease treated with aspirin were studied. All patients were randomly placed on 81mg, 162mg and 325mg of aspirin daily for four weeks each for a total of twelve weeks. Then, response to aspirin was tested by eight different methods. When methods were used that directly indicated the ability of aspirin to block its target, COX-1, it was found to be highly effective. Aspirin resistance was only observed in 1-5% of patients. However, when we used less direct methods to indicate the blockade of COX-1, we found that up to 30% of patients displayed resistance to at least one dose.

"The occurrence of thrombosis in patients during aspirin therapy has been attributed to failure of aspirin to block its target and is a pivotal topic in cardiovascular disease. However, our data suggest that aspirin blocks its target, COX-1 with high efficiency," said Dr. Paul Gurbel, lead investigator for the study and Director of Cardiology and Cardiovascular Research at Sinai Hospital of Baltimore in Maryland and Associate Professor of Medicine, Johns Hopkins University School of Medicine. "Aspirin resistance has been overestimated by tests that do not take into consideration the activity of COX-1. Further research is now underway to better understand alternate mechanisms underlying the occurrence of thrombotic events in patients on aspirin therapy in an effort to continue to improve patient outcomes".

This study is the largest thus far to compare multiple tests of aspirin's efficacy. The results strongly suggest that platelet aspirin resistance is overestimated by tests that do not directly reflect the level of aspirin's ability to block its target, COX-1. These results suggest that when measuring COX-1 inhibition with specific methods, aspirin is a very effective drug at all doses.