RC Block¹, L Kakinami¹, M Jonovich¹, I Antonetti¹, P CalderonArtero¹, N Meednu¹, S Mousa², S Georas^1
1University of Rochester, Rochester, United States of America
²Pharmaceutical Research Institute, Albany, United States of America

Background: Aspirin inhibits platelet function by acetylating cyclooxygenase, downregulating the production of thromboxane from arachidonic acid. Although aspirin has been a stalwart drug for the prevention and treatment of cardiovascular disease, many individuals do not benefit from its use: a problem termed “aspirin resistance”. Objective: As eicosapentaenoic acid and docosahexaenoic acid (EPA/DHA) are competitive inhibitors for cyclooxygenase, we investigated whether EPA/DHA enhances the effect of aspirin on platelet function in a group of healthy adults.

Procedure: We conducted a blinded, randomized, placebo-controlled, clinical trial in 25 healthy individuals. Each subject received a single dose of all of the following agents at 4 study visits at least 4 weeks apart: placebo; 81 mg aspirin; 3.4 g of EPA+DHA (4 g Lovaza®; n-3 long-chain polyunsaturated fatty acid {lcPUFA}); and both EPA+DHA and aspirin. On the evening prior to each appointment, each ate a consistent low-fat dinner, fasted for 8 hours, then ate a low-fat breakfast after each agent dose. Platelet function was measured with the Platelet Function Analyzer-100 (PFA- 100®), using closure time (CT) units (greater time indicates reduced platelet function), immediately before and 4 hours post agent. The Wilcoxon Signed Rank test was used to test for statistical significance.

Results: Compared to placebo, aspirin and Lovaza® alone had no significant effect on CT, but the combination of aspirin and Lovaza® increased CT by a mean of 34 seconds, from 131 to 165 (p=0.019). Conclusion: Our data suggest that low-dose aspirin and EPA+DHA exert a synergistic downregulatory effect on platelet function. Perhaps what is known as “aspirin resistance” may be more accurately described as “EPA+DHA deficiency”.

Keywords: lcPUFA, platelet function, aspirin resistance, EPA+DHA deficiency
Schlüsselwörter: Omega-3 Fettsäuren, Thrombozytenfunktion, Aspirin-Resistenz, EPA+DHA Mangel