Enteric Coating as a Factor in Aspirin Resistance

In a recent study we have shown clear evidence for pharmacokinetic aspirin resistance in healthy volunteers due to poor bioavailability of enteric-coated aspirin. However, it is necessary to confirm that pharmacokinetic resistance is an important factor in aspirin resistance in a patient population as well. To achieve this we will compare the response of patients to enteric-coated aspirin and plain aspirin in an open-labeled cross-over study in patients undergoing treatment with enteric-coated aspirin.

Patient population: Patients will be recruited from Dr. David Foley's clinic in Beaumont Hospital. All patients who have been prescribed enteric-coated aspirin (75 mg, any brand) will be considered eligible for enrollment providing they are competent to give informed consent. Patients of any diagnosis, any age and those on other medication will be considered eligible. Patients who are likely to stop aspirin therapy within a few weeks due to planned surgery or who are showing signs of adverse effects to aspirin will be excluded. Patients already enrolled in a clinical study will also be excluded.

Study design: After obtaining informed consent an appointment will be made with a patient to return to give a blood sample (ideally 1-2 weeks). The patient will be reminded of the importance of compliance and asked to keep a diary of aspirin use. On the scheduled visit a blood sample will be taken and the patient will be advised to keep taking their aspirin and that they would be advised of the outcome of the test within a week.

After the platelet function assessment those patients with adequate inhibition of platelet function will be informed that their aspirin dose is fine, reminded of the importance of compliance and their role in the study terminated. Patients who do not meet the target level of inhibition will be asked to return to the hospital where they will be switched to plain aspirin. They will be asked to return after two weeks for a further visit. Platelet function will then be assessed again. If the target inhibition is achieved they will be terminated from the study and with the agreement of their physician they will be switched to plain aspirin for future use. Those patients who do not achieve the target inhibition will be switched to 150 mg plain aspirin daily. A final escalation to 300 mg will used if necessary.

Platelet function tests Serum thromboxane. The gold-standard test of aspirin effects will be serum thromboxane production as determined by ELISA. A 5ml blood sample will be collected into a serum tube and incubated at 37ºC for 30 mins. The tube will then be centrifuged and the serum removed and frozen at -20ºC until analysed. In a previous study the baseline serum thromboxane levels in healthy volunteers was 276±99 ng/ml (±SD; n=142) and thus 95% inhibition would represent 13 ng/ml. We have previously shown that a serum thromboxane value of 2.2 ng/ml is a more effective marker of platelet function. This test will be unaffected by other medications except for anti-coagulants such as warfarin.