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Diabetes Ups Aspirin Resistance- More May Be Needed

Posted: Thursday, April 05, 2007

Aspirin resistance is more common among diabetics patients than nondiabetics, potentially requiring higher doses then Low-Dose asprin for adequate protection against a heart attack, researchers said.
Resistance to low-dose aspirin recommended for cardioprotection was found among 13% to 37% of patients with diabetes but only 3% to 14% of nondiabetic patients with a history of coronary artery disease, said Paul A. Gurbel, M.D., of Sinai Hospital and Johns Hopkins in Baltimore.

Testing by platelet aggregation or thromboxane metabolite generation showed that increasing the dose to 162 mg or 325 mg eliminated the difference between groups, he reported at the American College of Cardiology meeting.

"The one size fits all mentality is not really appropriate in diabetic patients," Dr. Gurbel said. "In selected diabetic patients baby aspirin is not enough."

However, further evidence from larger studies would be needed before routine high-dose aspirin -- which increases bleeding risk -- or routine aspirin resistance testing could be recommended for patients with diabetes, he cautioned.

Nevertheless, the results suggest aspirin resistance testing may be useful for individual diabetic patients, commented Robert S. Rosenson, M.D., of Northwestern University in Chicago, who moderated a press conference during which the study was discussed.

"We know that many individuals who are on aspirin therapy still have a heart attack, still have a stroke," Dr. Rosenson said. "How can we better help these individuals? How can we individualize the therapy? Perhaps measuring tests of platelet function in getting the right aspirin dose for that individual patient."

The double-blind, crossover study included 120 stable outpatients with a history of coronary artery disease treated with 81 mg, 162 mg, and 325 mg aspirin daily for four weeks. Thirty of the patients had diabetes, type 2 for most of them.

Platelet aggregation was evaluated after each dose period using blood and urine samples in four methods. Compliance was also strictly monitored.

Aspirin resistance was defined according to standard platelet aggregation or thromboxane metabolite generation cutpoints for each of the tests.

Among the aspirin resistance findings, the researchers reported:

For the lowest dose, rates ranged from 13% to 37% for diabetics and from 3% to 14% for non-diabetics, a statistically significant difference according to all but one of the tests (P=0.052, P=0.02, P=0.02, and P=0.002).

For the 162-mg dose, rates ranged from 3% to 23% for diabetics and from 3% to 13% for nondiabetics.
For the 325-mg dose, rates ranged from 3% to 23% for diabetics and from 0% to 16% for nondiabetics.
The overall efficacy of aspirin in reducing platelet aggregation was lower for diabetics than nondiabetics at the lowest dose only. For the 81-mg dose, aggregation was about 50% for diabetics compared with about 30% for nondiabetics. At the 162 mg and 325 mg, agreggation was about 30% for both diabetics and nondiabetics (P<0.001 versus 81 mg among diabetics).

"The dose dependent effects of aspirin suggest that the antithrombotic properties of the drug are not all explained by COX-1 inhibition," Dr. Gobel said.

He speculated that vessel-wall components, such as collagen, may be involved.

Practice Pearls: Explain to interested patients that diabetes may impact the efficacy of aspirin, but further studies would be needed before routine aspirin testing or routine high-dose aspirin could be recommended for diabetic patients.

Source: Diabetes In Control: Presented at the 56th annual scientific session of the American College of Cardiology (ACC). [Presentation title: Effects of Diabetes on the Prevalence of Aspirin Resistance During Low Dose Aspirin Therapy. Abstract 1019-179]