Aspirin resistance found to raise risk for heart attack, strokes

Testing patients for resistance is becoming more common, but it's not clear how useful this information is or what to do with it.

By Victoria Stagg Elliott — Posted Sept. 3, 2007

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Assessing platelet response to aspirin may help answer the question of why so many patients taking this drug have recurrent heart attacks and strokes and indicate who is in need of alternative preventive strategies, according to a study in the Archives of Internal Medicine last month.

Numerous papers have found that low-dose aspirin, a long-standing cornerstone of secondary prevention, does not equally affect everyone's blood, but no study has been large enough to determine if this variation translates to an increased risk of a cardiovascular event.

Researchers pooled 16 such studies and found that laboratory-defined aspirin resistance translated to a significantly higher chance of being sickened or killed by heart disease.

"Apparently, 'one dose of aspirin fits all' may not hold for antiplatelet therapy and, consequently, individually tailored therapy may be warranted," said Jaapjan D. Snoep, lead author and a research fellow in the Dept. of Clinical Epidemiology at the Leiden University Medical Center in the Netherlands.

Those investigating this issue criticized the analysis for combining studies with a great deal of heterogeneity. Patients had an array of cardiovascular conditions, and the studies reported many different endpoints. But experts praised it for adding to an increasingly controversial topic: How common is aspirin resistance, and what does it mean for patients and physicians?

"This adds another brick in the wall of knowledge that's indicating that aspirin resistance is an important and relevant clinical phenomenon," said Mark Alberts, MD, director of the stroke program at Northwestern Memorial Hospital in Chicago. He is studying the phenomenon in his patient population.

Several tests for aspirin resistance are available, although they are used more often in research than in the clinical setting. Many physicians say they use them rarely, primarily because standardization is lacking across tests, and it can frequently be clear when aspirin is having an effect.

"Very often when people take aspirin they notice that they're bleeding or bruising more easily with trauma. Men notice after they shave in the morning that the aspirin is working," said Jeffrey Borer, MD, the Gladys and Roland Harriman professor of cardiovascular medicine at Weill Cornell Medical College in New York.

"If there's no evidence of bleeding, then I think it's probably worthwhile checking," said Dr. Borer

It's also unclear exactly what to do with this information, although research is beginning in this area.

Some physicians suspect that increasing aspirin dose or switching to another antiplatelet therapy may be reasonable.

"There are things you can do. None of them are proven," said Dr. Borer.

These possibilities are not without risk. Higher doses of aspirin can increase the odds of a gastrointestinal event. Other blood-thinning drugs can mean more expense for an unknown benefit, and patients may be resistant to those, too.

"The danger here is that changes to medical therapy will be made based on assays [for which the] clinical utility has not been established," said Dr. Andrew O. Maree, an interventional cardiologist at Boston University Medical Center.

"Aspirin dose may be increased inappropriately, putting the patients at a greater risk of a GI bleed. Clopidogrel may be added to aspirin inappropriately," said Dr. Maree

Find the problem's true extent

This lack of a widely accepted test along with a definition of aspirin resistance has also been a barrier to determining the true extent of the problem. Scientific papers that have attempted to do so have found rates ranging from 5% to 45%, and a study in the June 26 Circulation found a prevalence from 0% to 27%, depending on the assay used.

"The determination of aspirin resistance is wholly dependent on the assay and the definition of aspirin resistance that you start out with," said Paul Gurbel, MD, lead author on that paper and director of the Center for Thrombosis Research at Baltimore's Sinai Hospital.

Many who work in cardiovascular health suspect that aspirin resistance is a more complicated matter than just having it or not, although this too is poorly understood.

"I think what we're dealing with is a continuum of response rather than a categorical yes or no," said Dr. Maree.

In addition, science identifying the root cause or mechanism of aspirin resistance, which most likely varies from patient to patient but could determine how it is addressed, is lacking. Several studies have suggested a wide array of possibilities, such as the impact of co-morbidities such as diabetes, as well as genetics, gender, weight and age. Patients may be more aspirin resistant on some days than others because of other drugs taken, a response to surgery or not taking the drug as directed.

"There's always a possibility that people are not taking it. The first question to ask, 'are you taking your drugs?' " said Robert O. Bonow, MD, chief of cardiology at Northwestern Memorial Hospital in Chicago. "But it could be genetics. It could be the other drugs that have an additive effect."

Experts say a better understanding of this phenomenon is crucial because so many people on secondary preventive regimens still have events. And, as suggested by this study, those who exhibit aspirin resistance are at much higher risk. Many would like to see a large prospective, randomized clinical trial to better assess the meaning of this kind of testing, determine how stable this phenomenon is over time and measure the effect of changing medication regimens in response to it.

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Aspirin resistance: Study findings

Objective: Does persistent platelet reactivity detected by laboratory testing in patients taking aspirin for secondary prevention contribute to an increased risk of a cardiovascular event?

Methods: Researchers pooled 16 studies of patients using aspirin to prevent a recurrent cardiovascular event. All included information about drug resistance.

Results: Patients with aspirin resistance had significantly greater odds of having a cardiovascular event compared with aspirin-sensitive patients.

Conclusions: This systematic review and meta-analysis shows that aspirin resistance as determined by laboratory testing is clinically meaningful.

Source: Archives of Internal Medicine, Aug 13/27

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External links

"Association of Laboratory-Defined Aspirin Resistance With a Higher Risk of Recurrent Cardiovascular Events," abstract, Archives of Internal Medicine, Aug. 13/27 (link)

"Evaluation of Dose-Related Effects of Aspirin on Platelet Function," abstract, Circulation, June 26 (link)

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