The Effects of Omega-3 Fatty Acids on Aspirin Resistance
Condition: Increased Drug Resistance
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to determine if omega-3 fatty acids enhance the antiplatelet
      effects of aspirin.
    

Detailed description: 
      Although aspirin has been a stalwart treatment in the prevention and treatment of myocardial
      infarction and stroke, it does not have its expected effects in a significant proportion of
      the population. This phenomenon has been termed "aspirin resistance". Omega-3 fatty acid
      supplementation has been associated with a reduced risk of sudden cardiac death and
      myocardial infarction. The beneficial effects of omega-3s are considered to be partially due
      to their ability to prevent platelet aggregation. However, the ability of omega-3s to enhance
      the effects of aspirin in those who suffer from aspirin resistance has not been determined.
      It is known that aspirin stimulates the production of potent lipid mediators from omega-3
      fatty acids and that these mediators have powerful antiinflammatory and tissue-protective
      effects. Thus, the treatment of individuals at high risk for myocardial infarction and stroke
      with both aspirin and a pharmaceutical-grade omega-3 fatty acid medication may be a powerful
      combination in the prevention and treatment of life-threatening cardiovascular disease.

      Study Protocol: Non-smoking male and female subjects between the ages of 18 and 50 not taking
      any medications, vitamin pills, nutritional supplements, or herbal preparations were
      recruited. Subjects with a history of chronic diseases (e.g. cardiovascular, renal, hepatic,
      neurodegenerative, neoplastic, metabolic {diabetes}, hypertension; based on screening medical
      history, a complete blood count, and comprehensive metabolic profile), or allergic reactions
      to aspirin, fish, fish oils, or non-steroidal anti-inflammatory drugs were excluded. Other
      exclusions included drinking more than three alcoholic beverages a day, or having any of the
      following conditions: an ulcer or bleeding in the stomach, liver or kidney disease, bleeding
      or blood clotting disorder (e.g. hemophilia), congestive heart failure, fluid retention, high
      blood pressure, gout, asthma, arthritis, or nasal polyps. This was a randomized,
      placebo-controlled, double-blinded trial with a cross-over design. Each subject served as
      his/her own control. The study involved four visits four weeks apart, all hosted in the
      University of Rochester Clinical Research Center. At each separate study visit, each subject
      received (using a randomized protocol) placebo, 81 mg aspirin, 4 g Lovaza(R)(3.4g of
      EPA+DHA), or both aspirin and Lovaza(R). Thus, each subject received each of these treatments
      individually in a random fashion over the four visits. Subjects, Center staff, and
      investigators were blinded as to which treatment was given at each visit and this ensured by
      the study pharmacist making the tablets and capsules for each treatment appear identical.
      Prior to each visit, subjects ate a standard low-fat dinner the prior evening, then fasted
      for at least 8 hours prior to arrival at the Center. Subjects were required to abstain from
      taking aspirin or non-steroidal anti-inflammatory drugs for 10 days prior to each visit and
      omega-3 fatty acids for 30 days prior to the baseline study visit, and all subsequent clinic
      visits. Visits lasted approximately 6 hours, with subjects at bedrest. A venous catheter was
      placed in a peripheral vein (saline lock, 18 gauge or larger, {no heparin used} in the
      forearm) with blood drawn, at baseline and 4 hours post-treatment, into citrated tubes at
      each visit for Platelet Function Analyzer-100 (PFA-100-Siemens, Deerfield, IL) closure time
      testing. Subjects were provided with a standard low-fat breakfast after the baseline
      phlebotomy.
    

Intervention name(s): Aspirin; Lovaza; Both Aspirin and Lovaza; Placebo
Intervention type(s): Drug; Drug; Drug; Other
Intervention description(s): Aspirin 81mg tablet; Lovaza 4 grams; Lovaza 4 grams plus aspirin 81 mg; Capsule resembling fish oil and a tablet resembling aspirin
Other intervention name(s): ethyl EPA + DHA; fish oil; Lovaza and aspirin
Intervention MeSH terms: Aspirin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: aspirin; omega 3 fatty acids; Lovaza; myocardial infarction; aspirin resistance; cardiovascular disease