The Triglyceride Lowering Effect of an Omega-3 Fat (DHA) in Addition to Statin Therapy for Patients With CAD or Diabetes
Condition: Hypertriglyceridemia (TG>200<500); Hyperlipidemia; Coronary Artery Disease; Coronary Risk Equivalent; Diabetes
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Hyperlipidemias; Hyperlipoproteinemias; Hypertriglyceridemia
Study type: Interventional

Summary: 
      This study will explore the ability of an algae (ocean plant) omega-3 fat supplement (DHA) to
      reduce triglyceride levels in patients currently being treated with statin therapy (Zocor or
      simvastatin, Lipitor or atorvastatin, Pravachol or pravastatin, Crestor or rosuvastatin,
      etc.) for coronary artery disease(CAD)or risk equivalents (any of the following: heart
      attack, post angioplasty or stent, post coronary bypass surgery, angina, vascular disease,
      stroke or diabetes).

      The rationale for the study is based around the finding that patients with CAD have an
      approximately 20 % reduction in the risk of sudden death when treated with fish oil (DHA is
      one of the ingredients in fish oil). In studies of statin-based therapies, it has been
      observed that statins reduce the risk of coronary events 20-45%. There has not yet been
      research trials exploring the combination of the two ingredients (i.e., DHA plus statin) in
      patient treatment either to reduce recurrent cardiac events or to address another reported
      finding of fish oils to lower triglyceride levels (triglyceride is a form of "blood fat").
      This research project will be a pilot project to assess the safety and effectiveness of DHA
      "add-on" therapy in patients currently being treated with statins for CAD.

      The study hypothesis is to test the effectiveness of DHA as compared to placebo to lower
      triglyceride levels in the blood. This is a double-blinded randomized clinical trial.
    

Detailed description: 
      Omega-3 fatty acids (nPUFAs) have been embraced by Expert Panels and Guideline Committees of
      the American Heart Association as a result of randomized trials documenting reductions in
      cardiovascular events in patients with coronary artery disease. The antiarrhythmic effect or
      a modification in the atherogenicity of lipoprotein particles by nPUFA treatment are
      speculated mechanisms of action. Although precise bioactivity is not clear, nPUFAs have been
      demonstrated to lower triglyceride (TG) levels. TG reductions have also been demonstrated in
      three randomized clinical trials where nPUFAs in the form of fish oil containing both
      eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) have been added to ongoing statin
      therapy.

      There are at least 8 large randomized clinical trials that have utilized statin agents as
      monotherapy to reduce cardiovascular events in patients with CAD. These trials have included
      more than 50,000 patients. The National Cholesterol Education Program (NCEP) recently
      released a "white paper" further reducing the LDL treatment target to 70 mg% as a result of
      four recently published trials. Although cardiovascular events rate and mortality reduction
      of 20-30% have been described, there is still a sizable number of patients experiencing
      untoward outcomes in spite of ongoing statin therapy. A variety of mechanisms of disease
      progression have been speculated including ongoing inflammation, insulin resistance and
      specific species of lipoprotein particles including HDL and LDL sub-classes. There has been
      recognition by the NCEP that beyond the treatment with statin therapies less tested methods
      of therapy might need to be applied. These therapies have included the lowering of
      triglycerides.

      It is the purpose of this pilot study to explore the relationship of DHA as a strategy for
      triglyceride lowering in CAD patients receiving on-going statin therapy and candidates for
      the yet (untested) recommendation by NCEP of the need to lower triglyceride levels exceeding
      200 mg% in statin-treated individuals.

        1. This is a single-center, prospective, randomized, double-blinded, placebo-controlled,
           parallel-group clinical trial of Martek's DHASCO™ versus placebo in subjects with CAD or
           risk equivalents (including type II DM)

        2. There will be a 4-wk run-in period to assure both diet and triglyceride stabilization.

        3. After the base-line run-in period, if triglyceride levels exceed 200 mg% they will be
           eligible to procede with the intervention either placebo or 2 grams of DHA

        4. Patients will be treated for an 8 week period. Visits will occur every other week during
           the treatment cycle.

        5. Laboroatory parameters to be followed during the course of the clinical trial includes:
           beta quantification of lipids, NMR particle analysis of lipoprotein particle size,
           apoprotein genotyping and other basic chemistry measurements
    

Intervention name(s): docosahexanoic acid (DHA)
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Omega-3; Triglyceride; Hyperlipidemia; Coronary Artery Disease; Fatty Acids; Safety; Fish Oil; Docosohexanoic Acid