Treatment of Aspirin-Resistant Patients with Omega-3 Fatty Acids versus Aspirin Dose Escalation

Abstract

Conclusion: Aspirin resistance can be treated by increasing the aspirin dose or adding omega-3 fatty acids. Summary: There is a wide interindividual variability in aspirin response (Circulation 2002;105:1650-5). The prevalence of aspirin resistance or low response is estimated to be <1% to 45%. Aspirin resistance is associated with an odds ratio of almost 4 for development of cardiovascular events (BMJ 2008;336:195-8). It is unclear whether increasing the dose in patients with aspirin resistance will provide adequate antiplatelet effects or if an alternative strategy, such as adding additional substances that would inhibit the cyclooxygenase (COX)-1 pathway, would be effective. Omega-3 fatty acids, components of dietary fish oil, lead to replacement of n-6 fatty acids, such as arachidonic acid (AA), by n-3 fatty acids in cell membranes. This leads to an increase in eicosapentaenoic acid (EPA). EPA competes with AA as a substrate of the COX-1 pathway, leading to inhibition of collagen-induced platelet aggregation and mild prolongation of bleeding time (Am J Clin Nutr 1997;65:1687-98s). The authors sought to determine whether addition of omega-3 fatty acids or increases in aspirin dose improves response to low-dose aspirin among aspirin-resistant patients. There were 485 patients with stable coronary artery disease treated with 75 to 162 mg of aspirin daily for at least 1 week screened for aspirin response with the VerifyNow Aspirin Assay. Aspirin resistance was defined by ≥2 of 3 criteria; VerifyNow score >550, 0.5 mg/mL AA-induced aggregation ≥20%, and 10 μmol/L adenosine diphosphate (ADP)-induced aggregation ≥70%. Thirty patients (6.2%) were aspirin-resistant and were randomized to receive either low-dose aspirin plus omega-3 fatty acids or aspirin at 325 mg/d. Patients were retested for aspirin activity 30 days later. After treatment, there were significant reductions in VerfiyNow scores and in AA-induced and ADP-induced platelet aggregation. Thromboxane B2 was also reduced in both groups (39.6% decrease in the aspirin group and 56.8% reduction in the omega-3 fatty acid group). After treatment, 12 patients (80%) who received omega-3 fatty acid and 11 (73%) who received aspirin at 325-mg doses were no longer aspirin-resistant. Comment: The article potentially provides a therapeutic approach to managing and overcoming aspirin resistance in patients treated with low-dose aspirin. One can either increase the aspirin dose or add omega-3 fatty acids to overcome aspirin resistance. The study is a pharmacologic study only. Larger studies will be required to assess whether the addition of omega-3 fatty acids to low-dose aspirin will translate into a clinical benefit in patients with cardiovascular disease resistant to low-dose aspirin. Given that many patients cannot tolerate 325 mg of aspirin daily, one wonders if there is any downside to just adding omega-3 fatty acids to the medication regimen of patients treated with low-dose aspirin?