Do Fish Oils Prevent Restenosis Post-Coronary Angioplasty?
Condition: Cardiovascular Diseases; Coronary Disease; Heart Diseases; Myocardial Ischemia
MeSH terms: Cardiovascular Diseases; Heart Diseases; Coronary Disease; Myocardial Ischemia; Ischemia
Study type: Interventional
Phase: Phase 3

Summary: 
      To determine whether a dietary supplement of n-3 polyunsaturated fatty acids (PUFAs) derived
      from fish oil would decrease the restenosis rate in patients undergoing percutaneous
      transluminal coronary angioplasty (PTCA).
    

Detailed description: 
      BACKGROUND:

      Coronary angioplasty is a non-surgical means of mechanical coronary artery revascularization
      with the potential of reducing or eliminating severe coronary arterial narrowing which
      results in myocardial ischemia. Since its innovation, the technique of coronary angioplasty
      has undergone continuous refinement, so that a greater proportion of patients are now
      eligible for this increasingly successful procedure. All clinical syndromes associated with
      coronary artery disease, including chronic stable angina, silent myocardial ischemia,
      unstable angina, and acute myocardial infarction, have been successfully treated with this
      therapy, and often dramatic, favorable results are achieved. A persistent limitation of the
      procedure has been the development of restenosis or the recurrence of coronary arterial
      narrowing which usually occurs within six months of successful balloon dilatation, in spite
      of current treatments such as anti-platelet agents. Several clinical trials have attempted to
      identify pharmacologic regimens aimed at reducing the incidence of restenosis. With rare
      exception, these trials have failed to detect a positive effect of any drug intervention.
      Considering that restenosis reflects multiple factors, such as thrombosis, spasm, an
      exaggerated response to injury, smooth muscle cells, platelets, and components of arachidonic
      acid metabolism, multiple pharmacologic therapies have been employed, including aspirin,
      warfarin, heparin, calcium antagonists, and steroids.

      Investigators have directed attention to the potential role of marine polyunsaturated fatty
      acids as potential inhibitors of restenosis. Dietary fish oil has been shown to inhibit
      platelet aggregation and stimulate thromboxane synthesis, to reduce platelet vascular
      interactions in atherosclerotic and injured blood vessels, and to inhibit diet-induced
      atherogenesis in swine and in two species of monkeys. One study has shown that dietary fish
      oil administered to pigs reduced platelet deposition and vasoconstriction in balloon catheter
      induced carotid artery lesions. In addition, fish oil reduces blood and red cell viscosity
      and also inhibits the function of monocytes which may be important in the pathogenesis of
      atherosclerosis or in the vascular response to injury.

      Early reports from human studies have been mixed, with most investigations failing to
      demonstrate a positive effect. However, these trials have been limited to small numbers of
      patients and typically lacked the rigor of a randomized, controlled clinical trial with a
      hard endpoint and aggressive administration of fatty acids. N-3 PUFAs have been reported in
      humans to increase prostacyclin formation and plasma fibrinolytic activity and to reduce
      serum lipids, vascular reactivity, and the inflammatory potential of white blood cells at the
      site of vascular injury, factors potentially involved in restenosis post-PTCA. Therefore,
      there was some reason to believe that the addition of n-3 PUFAs to aspirin might have a
      greater effect upon restenosis of treated vessels than aspirin alone. The basis of this study
      rested with epidemiologic data from the Eskimos and Japanese that the ingestion of n-3 PUFAs
      derived from cold water marine sources has a favorable effect in preventing the development
      of coronary artery disease.

      DESIGN NARRATIVE:

      Randomized, double-blind. Patients at eight centers were assigned to receiving for six months
      a daily dietary supplement of fish oil (ten 1.0-g capsules containing 80.6 percent ethyl
      esters of omega-3 fatty acids providing 4.1 g eicosapentaenoic acid [EPA] and 2.8 g
      docosahexaenoic acid [DHA]) or to a control group receiving corn oil. The high dose of fish
      oil approached the intake of the Greenland Inuits and was chosen with the hope of overcoming
      any antagonistic effects of other fatty acids competing with those of EPA or DHA, such as
      arachidonic acid or saturated fats. Two weeks prior to PTCA, patients began to take the
      capsules. Aspirin was initiated 12 hours prior to PTCA and continued for six months. Dietary
      counseling was provided prior to the two week intervention. Upon admission for PTCA and one
      week following PTCA, expanded dietary counseling and instruction were given. Patients were
      telephoned monthly to reinforce dietary information which included the American Heart
      Association Phase I diet to reduce total fat to 30 percent of total energy. Diet was not
      rigidly controlled. Recruitment began in August 1989 and ended in September 1992. Patients
      exited from the trial upon completion of the protocol, including a final set of evaluations
      at six months. The primary endpoint was presence or absence of restenosis as defined by
      angiography six months after PTCA. The trial was extended without additional funds through
      June 1994 to allow data analysis.
    

Intervention name(s): dietary supplements; fatty acids, omega-3; diet, fat-restricted
Intervention type(s): Behavioral; Drug; Behavioral
Allocation: Randomized
Masking: Double
Primary purpose: Prevention