Omega-3: Fakten - Therapie und Dosierung
PTCA Restenosierung: Kein Erfolg mit n-3 PUFA
In Fachzeitschriften wurden folgende Artikel über Omega-3 publiziert. Die Liste dieser Publikationen wurde im April 2003 kompiliert und erhebt keinen Anspruch auf Vollständigkeit. Quelle: MEDLINE.
Die Daten dienen als Referenz für Ärzte und Therapeuten. Es gibt keine therapeutische Dosis vor oder nach Restenosierung, von hohen Dosen wird abgeraten.
Fish oils and low-molecular-weight heparin for the reduction of restenosis after percutaneous transluminal coronary angioplasty. The EMPAR Study.
Cairns JA: Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Gill J, Morton B, Roberts R, Gent M, Hirsh J, Holder D, Finnie K, Marquis JF, Naqvi S, Cohen E
Circulation 1996 Oct 94:1553-60
BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) is complicated by restenosis within 6 months in > 40% of patients. Theoretical, animal experimental, and human epidemiological and clinical trial findings have suggested that fish oils (n-3) might reduce restenosis. Low-molecular-weight heparin (LMWH) has reduced cellular proliferation and restenosis in several experimental systems. METHODS AND RESULTS: We randomized 814 patients to fish oils (5.4 g n-3 fatty acids) or placebo a median of 6 days before PTCA and continued for 18 weeks. At the time of sheath removal, 653 patients with at least one successfully dilated lesion were randomized to LMWH (30 mg SC BID) or control for 6 weeks in a 2 x 2 factorial design. Follow-up with quantitative coronary angiography (QCA; target, 18 weeks) was interpretable on 96% of these patients. Restenosis rates per patient were for n-3, 46.5%; placebo, 44.7%; LMWH, 45.8%; and control, 45.4%. Restenosis rates per lesion were for n-3, 39.7%; placebo, 38.7%; LMWH, 38%; and control, 40.4%. At follow-up QCA, mean minimal lumen diameters were (mm) for n-3, 1.12; placebo, 1.10; LMWH, 1.12; and control, 1.10. Fifteen percent of patients permanently discontinued n-3/placebo before study completion, and 21% of patients discontinued LMWH early. There were no significant differences in the occurrences of ischemic events. Bleeding was more common with LMWH, usually was mild, and led to early discontinuation of study medication in only 0.9% of patients. Gastrointestinal side effects were more common in patients receiving n-3 than placebo. CONCLUSIONS: There is no evidence for a clinically important reduction of PTCA restenosis in this trial by either n-3 or LMWH. Evaluation of the results for n-3 in the context of previously published data on the reduction of PTCA restenosis indicates that n-3 is not efficacious and that further trials are unwarranted.
n-3 fatty acids and revascularization procedures.
Arnesen H: Ullevål University Hospital, Oslo, Norway
Lipids 2001 36 Suppl:S103-6
Largely initiated by studies among Greenland Eskimos in the early 1970s, great attention has been given to the possible effects of the very long chain n-3 polyunsaturated fatty acids (PUFA) in a variety of cardiovascular disease states. A series of possibly positive effects on pathogenetic mechanisms in cardiovascular disease has evolved from laboratory studies in cell cultures and animals as well as in humans, focusing mainly on eicosanoid metabolism with reduced activities of platelets and leucocytes, reduced plasma triglycerides and, antiarrhythmic effects in the myocardium. A rationale for a positive effect of very long chain n-3 PUFA in the secondary prophylaxis after revascularization procedures obviously also exists. The positive clinical effects based on prospectively randomized trials are summarized as follows. After coronary artery bypass grafting (CABG), the SHOT study showed statistically significant reduction in angiographic vein graft occlusion in 610 patients after 1 yr with supplementation of 3.4 g/d of highly concentrated very long chain n-3 PUFA. The reduction in occlusion rates was significantly related to the change in the n-3 PUFA concentration in serum phospholipids during the study period with the occlusion rate in the upper quartile of such changes at only approximately 50% of that in the lower quartile. These results were also clearly related to the presence of angina pectoris and occurrence of myocardial infarction after 1 yr. Several studies were conducted in patients after percutaneous transluminal coronary angioplasty (PTCA). By 1993, two meta-analyses indicated a positive effect on the restenosis rate, a significant problem after otherwise successful PTCA. During the late 1990s, three large prospective randomized placebo-controlled angiographic studies were conducted with very long n-3 PUFA 5.1-8.0 g/d, all with completely negative results. Today, therefore, very long chain n-3 PUFA supplementation cannot be recommended to reduce the incidence of restenosis after PTCA. All studies were performed without stenting of the coronary lesion. In the very special revascularization procedure of heart transplantation, evolving hypertension and accelerated atherosclerosis have been major clinical problems. In other studies, positive effects by supplementation with very long chain n-3 PUFA (3.4-5.7 g/d) were obtained on the surrogate end points coronary vasoreactivity to acetylcholine and hypertension, respectively. On the basis of the presently available literature from clinical studies, recommendations for supplementation with very long chain n-3 PUFA can be given to patients after venous CABG (up to 3.4 g/d), and after heart transplantation (3.4-5.7 g/d) but not to patients after traditional PTCA. In fact, data from substudies suggested the possibility that large doses (5.1 g/d) of very long chain n-3 PUFA might be contraindicated because they induce a proinflammatory state in patients under oxidative stress.
Usefulness of fish oil supplements in preventing clinical evidence of restenosis after percutaneous transluminal coronary angioplasty.
Milner MR: Department of Medicine, Washington Hospital Center, Washington, DC, USA; Gallino RA, Leffingwell A, Pichard AD, Brooks-Robinson S, Rosenberg J, Little T, Lindsay J
Am J Cardiol 1989 Aug 64:294-9
This study assesses the effect of dietary supplements with high dose omega-3 fatty acid (N3FA) on the frequency of clinical restenosis during the 6 months after successful percutaneous transluminal coronary angioplasty (PTCA). One hundred ninety-four patients (214 significant coronary narrowings) were randomized after successful PTCA to receive conventional medical therapy or to an identical regimen supplemented by high dose N3FA (4.5 g/day). Enrollment required angina pectoris and successful dilatation of all significant coronary narrowings. The subjects were randomly assigned to either no N3FA (control, n = 99) or N3FA supplementation (n = 95). After a 1-week trial period, 11 (group 2) declined further treatment because of side effects. The remaining 84 subjects (group 1) continued N3FA throughout the 6-month period. Monthly clinical follow-up was obtained in all patients. Ninety-two percent of patients had cardiac testing for evaluation of recurrent ischemia. Except for a greater percentage of women in the group refusing N3FA supplementation (group 2), the 3 groups were similar in demographic data, medical history, dietary habits, history of previous PTCA and angiographic characteristics. Of the 194 subjects, 56 had clinical restenosis (45 by cardiac catheterization, 8 by exercise testing and 3 by symptoms alone [refused further clinical testing]). Reocclusion rates were: group 1 19%, group 2 46%, and control 35%. Analysis both in accordance with the principle of intention to treat and for subjects who actually received N3FA revealed a significant effect of N3FA on preventing clinical restenosis (p less than 0.04 and p = 0.008, respectively). These data suggest that high dose N3FA supplements reduce the clinical restenosis rate after successful PTCA.
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Randomised trial of fish oil for prevention of restenosis after coronary angioplasty.
Reis GJ: Charles A. Dana Research Institute, Boston, MA, USA; Boucher TM, Sipperly ME, Silverman DI, McCabe CH, Baim DS, Sacks FM, Grossman W, Pasternak RC
Lancet 1989 Jul 2:177-81
To examine the potential role of fish oil supplementation in the prevention of restenosis after coronary angioplasty (PTCA), a randomised double-blind trial was conducted in 204 patients. The treatment group received 6 g/day of n-3 fatty acids, beginning 5.4 (SD 3.2) days before PTCA, and continuing for 6 months; the control group received olive oil placebo. Compliance was assessed by pill count and plasma levels of eicosapentaenoic acid (EPA). Restenosis was identified by symptoms and exercise testing and confirmed by angiography. PTCA was successful in 186 patients (93%). The incidence of angiographic restenosis was 34% in the fish oil group and 23% in the control group (relative risk 1.7, 95% CI 0.9-3.4). The lack of benefit of fish oil was not influenced by length of pretreatment, compliance with study medication, or the concentrations of plasma EPA achieved.