Pharmacological Resistance to Aspirin In Patients with Stable Coronary Artery Disease.

Aspirin is the cornerstone of antiplatelet therapy in patients with coronary artery disease (Lancet 1997; 350: 437–439). However, a substantial proportion of patients manifest “breakthrough” events despite regular intake of aspirin suggesting therapeutic resistance to aspirin. Unfortunately, aspirin resistance remains a poorly defined term. There are conflicting reports on the prevalence of aspirin resistance in India.

We evaluated the prevalence of pharmacological resistance to aspirin therapy in patients with stable and unstable coronary artery disease at a tertiary center in India. One hundred and twenty six patients aged ≥21 with recorded history of previous myocardial infarction (MI) and/or angiographically proven coronary artery disease undergoing routine outpatient cardiac care were enrolled in the study. Eligible patients were recruited 7days after ensuring compliance with a single formulation of aspirin (enteric coated aspirin 150 mg). Compliance was determined by obtaining a history of drug ingestion and performing a pill count. Patients with history of bleeding disorders and those consuming clopidogrel, dipyridamole, or non-steroidal anti- inflammatory drugs were excluded from study. Platelet function analysis was performed using the technique of optical aggregometry (Chronolog 490D, PA, USA). The following agonists (concentrations in parenthesis) were used: ADP (5 μM), Arachidonic acid (0.5 mg/mL), Collagen (2 μg/mL), and Epinephrine (5 μM). A healthy control was run every time a batch of tests was run for subjects. Pharmacological aspirin resistance was defined as the combined demonstration of mean platelet aggregation of ≥ 70% with ADP and a mean aggregation of ≥20% with Arachidonic acid in patients compliant with aspirin therapy. Patients satisfying either one of the above criteria were considered semi-responders (Am J Cardiol 2001; 88:230-5).

Out of a total of 126 patients with stable CAD, 64 % were responders, 36 % were non responders (semi-responders = 34% and resistant = 2%). All the patients with acute coronary syndrome (n = 7) were found to be semi-responders. Aspirin resistance did not show any statistically significant correlation with CAD risk factors like history of smoking, diabetes, obesity and hypertension. Of the laboratory parameters, only the total leukocyte count was significantly associated with the presence of aspirin resistance (p<0.03). Surprisingly, this relationship did not extend to either the absolute lymphocyte or neutrophil count. The other laboratory parameters such as hemoglobin, platelet count, hematocrit, mean cell volume, total protein, and albumin did not show any significant statistical relationship with aspirin resistance. To overcome the influence of preanalytical variables, platelet aggregation studies were repeated randomly on 50% of the study population. Paired analysis did not reveal any major changes among the responders and semi responders although the two resistant patients became semi-responders.

Pharmacological resistance or semi-responsiveness to aspirin is prevalent in Indian patients with stable coronary artery disease. Long term follow up of these patients to ascertain their clinical outcome will assist in determining the clinical importance of this phenomenon.

No relevant conflicts of interest to declare.