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CLINICAL RESEARCH: ASPIRIN RESISTANCE

Treatment of Aspirin-Resistant Patients With Omega-3 Fatty Acids Versus Aspirin Dose Escalation

Eli I. Lev, MD^_*,,_*, Alejandro Solodky, MD^_*,, Naama Harel^_*, Aviv Mager, MD^_*,, David Brosh, MD^_*,, Abid Assali, MD^_*,, Milton Roller, MD^_*,, Alexander Battler, MD^_*,, Neal S. Kleiman, MD and Ran Kornowski, MD^_*,

^_* Cardiology Department, Rabin Medical Center, Petah Tikva, Israel
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Methodist DeBakey Heart Center, The Methodist Hospital, Houston, Texas

Manuscript received June 12, 2009; accepted August 10, 2009.

^_* Reprint requests and correspondence: Dr. Eli I. Lev, Rabin Medical Center, The Sackler Faculty of Medicine, 39 Jabotinsky Street, 49100 Petah Tikva, Israel (Email: elil{at}clalit.org.il).

Objectives: The aim of this study was to evaluate whether addition of omega-3 fatty acids or increase in aspirin dose improves response to low-dose aspirin among patients who are aspirin resistant.

Background: Low response to aspirin has been associated with adverse cardiovascular events. However, there is no established therapeutic approach to overcome aspirin resistance. Omega-3 fatty acids decrease the availability of platelet arachidonic acid (AA) and indirectly thromboxane A2 formation.

Methods: Patients (n = 485) with stable coronary artery disease taking low-dose aspirin (75 to 162 mg) for at least 1 week were screened for aspirin response with the VerifyNow Aspirin assay (Accumetrics, San Diego, California). Further testing was performed by platelet aggregation. 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 found to be aspirin resistant and randomized to receive either low-dose aspirin + omega-3 fatty acids (4 capsules daily) or aspirin 325 mg daily. After 30 days of treatment patients were re-tested.

Results: Both groups (n = 15 each) had similar clinical characteristics. After treatment significant reductions in AA- and ADP-induced aggregation and the VerifyNow score were observed in both groups. Plasma levels of thromboxane B2 were also reduced in both groups (56.8% reduction in the omega-3 fatty acids group, and 39.6% decrease in the aspirin group). Twelve patients (80%) who received omega-3 fatty acids and 11 patients (73%) who received aspirin 325 mg were no longer aspirin resistant after treatment.

Conclusions: Treatment of aspirin-resistant patients by adding omega-3 fatty acids or increasing the aspirin dose seems to improve response to aspirin and effectively reduces platelet reactivity.

Key Words: aspirin • omega-3 fatty acids • platelets

Abbreviations and Acronyms   AA = arachidonic acid   ADP = adenosine diphosphate   ARU = aspirin reaction units   CAD = coronary artery disease   COX = cyclooxygenase   EPA = eicosapentaenoic acid   MI = myocardial infarction   PCI = percutaneous coronary intervention   TXB2 = thromboxane B2

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