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.