Date of Award
MSc by research (Master of Science by research)
Dr Dermot Cox
Aspirin, Drug Resistance
Background: Low-dose aspirin is used for the prevention of thrombosis in the treatment of cardiovascular disease. Patients failing to respond to their aspirin are classified as Aspirin Resistant (AR) and are at a greater risk of having a cardiovascular event (CVE). Our study sets out to: evaluate aspirin response in a real world cardiovascular population, assess the utility of Platelet Function Tests (PFT's) in the clinic and identify causes of AR, with the overall aim of improving patient clinical outcomes.
Methods: Aspirin non-responding patients were identified using laboratory based methods (Light Transmission Aggregometry with arachidonic acid, VerifyNow™-Aspirin, serum thromboxane B2) to screen a cardiovascular diseased patient population. Interventions (interview and education) were used to encourage and ensure compliance and aspirin brands were switched from 75 mg enteric-coated to 75 mg un-coated and increased to a max. dose of 300 mg un-coated aspirin until premium in vitro aspirin response was achieved by all three assays.
Results: 248 (65±10yr, 79±14kg) patients were screened for their response to aspirin by at least one of three in vitro platelet function tests. 29% (71 patients) (64±13yr, 87±18kg) were identified as non-responding. 16% of the cohort (41 patients) (65±12yrs, 85±16kg) responded to aspirin following interventions to improve compliance. After ensuring patient compliance, only 6% (1 6 patients) (57±12yr, 98±23kg), all taking 75 mg enteric coated aspirin, remained non-responsive and were switched to 75 mg un-coated aspirin and increased to 300 mg un-coated aspirin until optimum aspirin response achieved. All but 0.4% (1 patient) responded. 6% of the entire cohort (16 patients) were lost to follow-up.
Conclusion: Our study shows that patient non-compliance is the primary cause of AR, accounting for 58% (41 patients) of perceived "resistance". With compliance assured, 6% of the cohort, one-in-four patients >90 kg, show an insufficient response to, and are thus unsuitably protected by, 75 mg enteric-coated aspirin. These heavier patients are not resistant to aspirin as they respond following substitution to 75 mg un-coated aspirin. In some cases (in 12.5% of patients >I00 kg) increasing to 150 mg un-coated aspirin is required to achieve cardiovascular protection. These data show that the maximum prevalence of true AR is 1.5% (95% confidence interval).
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McCall M. Aspirin "resistance" : an evaluation and explanation [MSc Thesis]. Dublin: Royal College of Surgeons in Ireland; 2010.