Determinants of restenosis and lack of effect of dietary supplementation with eicosapentaenoic acid on the incidence of coronary artery restenosis after angioplasty

Abstract

The effect of an eicosapentaenoic acid-rich encapsulated preparation of fish oil on the incidence of early restenosis after coronary angioplasty was assessed by a randomized double-blind placebo-controlled study. A total of 108 patients received either 10 capsules of fish oil (1.8 g eicosapentaenoic acid, 1.2 g docosahexaenoic acid) or 10 control capsules (50% olive oil, 50% corn oil), commencing the day before angioplasty and continuing for 4 months after angioplasty, in addition to treatment with aspirin and verapamil. In 101 (94%) of the 108 patients, follow-up angiographic or postmortem result was evaluated at a mean (+/- SD) of 100 (+/- 22) days. Angiographic restenosis was observed in 34% of patients (29% of lesions) in the fish oil-treated group and 33% of patients (31% of lesions) in the control group (no significant difference). The overall incidence of angiographic restenosis was significantly higher in patients with 1) recurrent angina pectoris, 2) a positive exercise test at follow-up after angioplasty, 3) residual stenosis greater than 30% immediately after angioplasty, and 4) dilation of the left anterior descending or right coronary artery. Biochemical investigations showed a greater decrease in the serum triglyceride levels in the fish oil-treated group versus the control group (p less than 0.05) but no differences between the two groups in cholesterol levels or platelet counts over the 4 month period. In conclusion, in this study, the administration of fish oil at a dose of 10 capsules/day did not reduce the incidence of early restenosis after coronary angioplasty.

Pharmacologic Intervention to Prevent Hemodialysis Vascular Access Thrombosis

“…Although we have been the only group to investigate EPA for the prevention of intimal hyperplasia and access thrombosis in hemodialysis patients, there have been sev eral studies of the use of EPA to prevent intimal hyperplasia and stenosis after angioplasty that are divided between those claiming benefit [72,73] and those finding none [74,75]. While this is disappointing, it is not unexpected since EPA produces its effect through competitive inhibition ( fig.…”

Clinical trials of restenosis after coronary angioplasty.

“…6 Unfortunately, multiple pharmacological strategies aimed at prevention of restenosis have thus far failed to demonstrate a convincing reduction in its incidence. [7][8][9][10][11][12][13][14][15][16][17] The profound economic importance of the identification of an agent or combination of agents that will reduce restenosis after coronary angioplasty has led to an impressive investment of resources into clinical restenosis trials. Because the number of agents that can be tested in this setting is exceptionally large, for descriptive purposes, these agents can be divided into those that primarily inhibit platelet-specific receptors, platelet mediators, and thrombus formation at the site of coronary angioplasty; smooth muscle cell proliferation; and growth factors ( Figure 1).…”

Fish oil and the prevention and regression of atherosclerosis

“…Pretreatment with fish oil appears relevant as it takes weeks for the ingested 20:5n-3 and 22:6n-3 to be incorporated into the cell membranes and platelet deposition with subsequent local release of growth factors occurs very early after balloon injury of a vessel. Of the five studies without pretreatment two are negative [88,92], two [86,91] are positive and one [90] is positive based on clinical restenosis rate but negative when assessed by subsequent selective coronary angiography. On the other hand, two studies [89,94] are -3); FO, fish oil-treated group of patients; control, control group; none vessel disease; bmultivessel disease; ¢based on "intention to treat" principle; d%lesions/%lesions; e17% in aspirin/dipyridamole-treated patients.…”

“…Angiography seems to be the most appropriate approach as restenosis is observed angiographically in 11-33% of patients without symptoms or with the negative exercise tests [95]. Coronary angiography was conducted in almost all patients in four studies [87,88,91,93] and selectively in four [89,90,92,94], while in the study by Slack et al [86] only exercise tests were evaluated. O'Connor and colleagues have recently performed a meta-analysis of seven [86][87][88][89][90][91]94] studies (see also Table 6) [96] and concluded that fish oil yields a small to moderate reduction in restenosis rate (6-46%).…”

“…Table 6 contains all restenosis studies [86][87][88][89][90][91][92][93][94] with fish oil published in the English literature. With the exception of the study by Bowles et al [92] all studies include a control group.…”