The Effects of Omega-3 Fatty Acids on Aspirin Resistance

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

Study Overview

• Status: Completed
• Conditions: Increased Drug Resistance
• Intervention / Treatment: Drug: Aspirin; Drug: Lovaza; Drug: Both Aspirin and Lovaza; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester School of Medicine and Dentistry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willing to participate by providing informed consent and committing to complete the study. This includes adhering to the study diet.
• No chronic disease by history and based on a complete blood count and comprehensive metabolic profile.
• Commitment to not taking aspirin, non-steroidal anti-inflammatory medications, and to limit fish intake to ≤2 meals during the 7 days prior to each CRC study period. They will also need to abstain from taking a list of over-the-counter medications that include aspirin. For the duration of the study, they will also be asked to abstain from taking fish and flax seed oil supplements.

Exclusion Criteria:

• Reports the presence of chronic disease (e.g. cardiovascular, renal, hepatic, neurodegenerative, neoplastic, metabolic {diabetes}, hypertension).
• Reports taking a systemic medication chronically.
• History of serious adverse reaction or allergy to aspirin or fish oil.
• Baseline platelet count <100 000 or >500 000, hematocrit <30%, or white blood cell count >20 000.
• Any abnormality from a screening CBC and complete blood count that suggests acute or chronic disease.
• Nicotine user.
• History of alcohol abuse
• Pregnancy by history or urine/serum pregnancy test
• History of intestinal malabsorption syndrome including gastric bypass surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo, Lovaza, Aspirin, Both Aspirin and Lovaza; First Placebo, then 4 grams of Lovaza, then 81mg of Aspirin, then both 4 grams of Lovaza and 81 mg of Aspirin	Drug: Aspirin; Aspirin 81mg tablet; Drug: Lovaza; Lovaza 4 grams; Other Names: ethyl EPA + DHA; fish oil; Drug: Both Aspirin and Lovaza; Lovaza 4 grams plus aspirin 81 mg; Other Names: Lovaza and aspirin; Other: Placebo; Capsule resembling fish oil and a tablet resembling aspirin
Experimental: Aspirin, Lovaza, Both Aspirin and Lovaza, Placebo; First 81mg of Aspirin, then 4 grams of Lovaza, then both 81mg of Aspirin and 4 grams of Lovaza, then placebo	Drug: Aspirin; Aspirin 81mg tablet; Drug: Lovaza; Lovaza 4 grams; Other Names: ethyl EPA + DHA; fish oil; Drug: Both Aspirin and Lovaza; Lovaza 4 grams plus aspirin 81 mg; Other Names: Lovaza and aspirin; Other: Placebo; Capsule resembling fish oil and a tablet resembling aspirin
Experimental: Lovaza, Both Aspirin and Lovaza, Placebo, Aspirin; First 4 grams of Lovaza, then both 81mg of Aspirin and 4 grams of Lovaza, then placebo, then 81mg of Aspirin	Drug: Aspirin; Aspirin 81mg tablet; Drug: Lovaza; Lovaza 4 grams; Other Names: ethyl EPA + DHA; fish oil; Drug: Both Aspirin and Lovaza; Lovaza 4 grams plus aspirin 81 mg; Other Names: Lovaza and aspirin; Other: Placebo; Capsule resembling fish oil and a tablet resembling aspirin
Experimental: Both Aspirin and Lovaza, Placebo, Lovaza, Aspirin; First both 81mg of Aspirin and 4 grams of Lovaza, then placebo, then 4 grams of Lovaza, then 81mg of Aspirin	Drug: Aspirin; Aspirin 81mg tablet; Drug: Lovaza; Lovaza 4 grams; Other Names: ethyl EPA + DHA; fish oil; Drug: Both Aspirin and Lovaza; Lovaza 4 grams plus aspirin 81 mg; Other Names: Lovaza and aspirin; Other: Placebo; Capsule resembling fish oil and a tablet resembling aspirin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the Difference Between the Time to Clot Formation in Seconds at Baseline and After Each Treatment	The PFA-100 test measures platelet function as the time that it takes for a clot to form in a collagen-lined cartridge.	4 hours

Collaborators and Investigators

• Sponsor: University of Rochester
• Collaborators: GlaxoSmithKline; Cornell University; American College of Clinical Pharmacy
• Investigators: Principal Investigator: Robert C Block, MD, MPH, University of Rochester

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: October 14, 2008
• First Submitted That Met QC Criteria: October 14, 2008
• First Posted (Estimate): October 15, 2008

Study Record Updates

• Last Update Posted (Estimate): November 6, 2012
• Last Update Submitted That Met QC Criteria: October 31, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: cardiovascular disease; myocardial infarction; aspirin; aspirin resistance; omega 3 fatty acids; Lovaza
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: Study Protocol 112421