Omacor (now Lovaza) is a pharmaceutical omega-3 fatty acid product. Omega-3 fatty acids can
affect blood clotting by altering the function of the blood platelets. Aspirin can do the
same. The purpose of this study is to determine the individual and combined effects of these
two agents on platelet function using a whole blood method.
This study will explore the effects of 4 g/d of Omacor in healthy volunteers both with and
without concomitant aspirin therapy. The study will utilize three different analytical
approaches to assess platelet activation and function.
The purpose of this exploratory study is to gather preliminary information on the effects of
Omacor on a platelet function in healthy volunteers, both with and without concomitant
aspirin therapy, in order to lay the groundwork for future studies in cardiac patients
taking Omacor in combination with aspirin and clopidogrel.
Omacor (omega-3 fatty acid ethyl esters) is approved for treatment of severe
hypertriglyceridemia, and may soon be approved for the treatment of moderate
hypertriglyceridemia in combination with statins. In other words, the use of Omacor will
continue to expand. The package insert notes that physicians should be attuned to the
possibility of increased bleeding tendencies with high dose (4 g/d) Omacor use despite the
fact that clinically significant bleeding has virtually never been reported with this dose
(or even up to 7 g of EPA+DHA) in studies in patients on concomitant anti-platelet therapy
undergoing highly invasive vascular procedures (e.g., diagnostic catheterization,
angioplasty, coronary artery bypass grafting). Nevertheless, because omega-3 fatty acids are
known to inhibit platelet function and to increase bleeding times(1), it is prudent to
explore and carefully define the effects of this dose of Omacor on platelet composition and
Primary and Secondary Endpoints
The primary endpoint will be the effects of Omacor ± aspirin on platelet aggregation
measured by whole blood impedence aggregometry in Harris's laboratory.
The secondary aims are to explore some of the molecular mechanisms by which omega-3 fatty
acids and/or aspirin may alter platelet function. These include spreading assays, and tests
of calcium and ATP release (described below). Even if the whole blood aggregation assays
are not altered by Omacor treatment (they will be altered by aspirin treatment), these tests
are sensitive to more subtle alterations in platelet function that could be missed in
platelet aggregation assays. Alternatively, omega-3 FAs could impact two independent
pathways in opposite directions, resulting in a cancelling out of the overall effect on
platelet aggregation. These more focused experiments will be conducted at Dr. Mark Larson's
laboratory at Augustana College.
Experimental Design and Methodology
Design This will be an open-label, pre- and post, 4-week trial. Blood will be drawn on day 1
(baseline), day 2 (1 day after taking 650 mg of aspirin), day 29 (after taking Omacor for 28
days), and day 30 (Omacor + 650 mg of aspirin). Platelet aggregation will be tested in each
Subjects Ten healthy volunteers will be recruited from among the staff of Sanford
Research/USD, Sanford School of Medicine, and Sanford Hospital; patients, students,
visitors, and subordinates of the investigators will not be eligible. Subjects may be male
or female and between the ages of 21 and 60, non-smokers, and taking no medications, vitamin
pills, nutritional supplements or herbal preparations. Subjects may not have a history of
allergic reactions to aspirin, fish or fish oils. Birth control pills are not allowed.
Subject cannot have an allergy to aspirin or to non-steroidal anti-inflammatory drug (NSAID)
such as ibuprofen (Motrin, Advil, others), naproxen (Aleve, Naprosyn, Anaprox, others),
indomethacin (Indocin), or ketoprofen (Orudis KT, Orudis, Oruvail), nabumetone (Relafen),
oxaprozin (Daypro), or tartrazine. Other exclusions include: 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, heart disease, high blood pressure,
gout, asthma, arthritis, or nasal polyps.
Laboratory Methods Blood will be drawn into sodium citrate for all tests. Three agonists
will be used in the whole blood aggregometry tests: thrombin, collagen and ADP(3). The
output of this instrument (Chronolog Whole Blood Aggregometer, model 504) is in ohms, with
higher impedance values indicating greater platelet aggregation. Because this test is
conducted in whole blood (i.e., erythrocytes present), it is thought to be the most
physiologically-relevant method for testing platelet function.
- Subjects may be male or female and between the ages of 21 and 60,
- Taking no medications, vitamin pills, nutritional supplements or herbal preparations.
- Subjects may not have a history of allergic reactions to aspirin, fish or fish oils.
- Birth control pills are not allowed.
- Subject cannot have an allergy to aspirin or to non-steroidal anti-inflammatory drug
(NSAID) such as ibuprofen (Motrin, Advil, others), naproxen (Aleve, Naprosyn,
Anaprox, others), indomethacin (Indocin), or ketoprofen (Orudis KT, Orudis, Oruvail),
nabumetone (Relafen), oxaprozin (Daypro), or tartrazine.
- Drinking more than three alcoholic beverages a day
- 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,
- heart disease,
- high blood pressure,
- arthritis, or
- nasal polyps.