Do Fish Oils Prevent Restenosis Post-Coronary Angioplasty?

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: