Results Vary by Type of Assay Used to Measure It
Barcelona—Aspirin resistance may be less common than previously believed. When using methods that measure the inhibition of cyclooxygenase (COX)-1, aspirin resistance at any dose in patients with stable coronary artery disease (CAD) is rare, said Paul A. Gurbel, MD, FACC, director of cardiology and cardiovascular research, Sinai Hospital, and associate professor of medicine at Johns Hopkins University, Baltimore, at the 15th World Congress of Cardiology.
In previous studies, up to one fourth of patients with CAD have been found to be aspirin resistant. However, many of the assays used in these studies did not specifically measure inhibition of COX-1, aspirin’s intended target.
“Aspirin resistance has probably been overestimated by tests that do not take into consideration the activity of COX-1,” said Dr Gurbel.
He studied 120 patients with stable CAD who were being treated with aspirin. They were randomly assigned to 81, 162, or 325 mg of aspirin daily for 4 weeks each, for a total of 12 weeks. The response to aspirin was measured by 8 methods 5 of them were COX-1 specific and 3 of them were COX-1 nonspecific.
“There was no uniformity in the detection of aspirin resistance at the 3 doses tested,” explained Dr Gurbel. “We found no clear relation of dose to aspirin resistance in the individual patient.”
When measuring with the COX-1—nonspecific assays, resistance was as high as 32% at the 81-mg dose of aspirin. With the COX-1–specific assays, resistance ranged from 0% to 5%; 2 of the 4 COX-1—specific assays showed 0% resistance at the 325-mg dose of aspirin.
The message is that clinicians should be careful when interpreting the prevalence of aspirin resistance indicated by COX-1—nonspecific point-of-care assays, he said.
Dr Gurbel also found that patients who had high platelet aggregation in response to arachidonic acid (Verify Now point-of-care assay) had exaggerated platelet aggregation in response to other stimuli as well. “This suggests that not only were their platelets not fully blocked by aspirin, but that other pathways causing clot formation were highly active,” he said. Platelet aggregation was less frequent with the higher doses of aspirin.
Patients who are resistant to multiple platelet agonists may represent a high-risk phenotype for thrombotic events, he added.
In a third study of 100 patients undergoing a repeat percutaneous coronary intervention (PCI), those who exhibited high platelet aggregation while taking aspirin and clopidogrel (Plavix) were at increased risk for a thrombotic event in the year following the procedure.
A total of 70% of the patients in this study who had an ischemic event had >50% platelet aggregation before their PCI, as measured by standard light transmittance aggregometry, said Dr Gurbel.
Whether or not every patient scheduled for a PCI should undergo platelet aggregation testing still needs to be studied in a prospective, large-scale study, he added. Furthermore, alternative antiplatelet strategies should be studied in patients who demonstrate high platelet aggregation in order to reduce their risk of post-PCI ischemic events.
In previous studies, up to 25% of patients with CAD have been found to be aspirin resistant.
Many of the assays used to assess resistance did not measure COX-1 inhibition, aspirin’s intended target.
With the COX-1—nonspecific assays, resistance was up to 32% with 81 mg aspirin. With the COX-1—specific assays, resistance ranged from 0% to 5%; 2 of the 4 assays showed 0% resistance with 325 mg aspirin.
Patients resistant to multiple platelet agonists may represent a high-risk phenotype for thrombotic events.
Be careful when interpreting a patient’s aspirin resistance if the assay used is not designed to measure COX-1 inhibition.