Fish oil for restenosis after angioplasty: a meta-analysis
ACP J Club. 1994 Jan-Feb;120:8. doi:10.7326/ACPJC-1994-120-1-008
Gapinski JP, VanRuiswyk JV, Heudebert GR, Schectman GS. Preventing restenosis with fish oils following coronary angioplasty. A meta-analysis. Arch Intern Med. 1993 Jul 12;153:1595-601.
To study whether fish oil (omega-3 fatty acids) reduces the rate of restenosis after percutaneous transluminal coronary angioplasty.
Studies were identified using MEDLINE (1980 to July 1992) with the terms fish oils, therapeutic use, recurrence, and coronary disease; Index Medicus; lists of American Heart Association conference abstracts; bibliographies of relevant papers; and contact with researchers who had requested fish oils for research purposes from the National Oceanic and Atmospheric Administration.
English-language studies were selected if they were randomized trials with restenosis measured by angiography or stress testing. Duplicate publications were excluded.
Study quality, number of patients treated, and rates of restenosis in both treated and control groups. Intention-to-treat analysis was used, and homogeneity was assessed.
7 studies with 886 patients were analyzed. Doses of fish oil ranged from 3 to 6.5 g/d, follow-up was 99 to 365 days, 4 studies used angiography-proven restenosis, and the restenosis rate (proportion of patients with restenosis) in the control groups was 23% to 48%. The absolute rate difference (ARD) in restenosis between the control group and the study group for the 4 studies using angiography was 13.9% (95% CI, 3.2% to 24.5%). 7 patients were needed to treat to prevent restenosis in 1 person. Stepwise linear regression showed that increasing doses of fish oil were associated with decreased restenosis (P < 0.03). The pooled ARD for 3 g of fish oil was 2%; for 4 g, 13%; and for 5 g, 25%. When the 3 studies that used stress testing to assess restenosis were combined with the studies that used angiography, a trend toward decreased restenosis was seen (ARD, 5.1%; CI, -3.8% to 13.9%). Minor gastrointestinal side effects occurred in 18% to 50% of patients who took fish oil and in 7% to 50% of those not treated or taking placebo. Serious bleeding occurred in 0% to 3% of patients taking fish oil and in none of the other patients.
Fish oils (omega-3 fatty acids) reduced angiographic restenosis after percutaneous transluminal coronary angioplasty. Increased benefit in restenosis was associated with increased doses of fish oil.
Source of funding: Not stated.
For article reprint: Dr. J.P. Gapinski, Division of General Internal Medicine, Medical College of Wisconsin, Zablocki Veterans Affairs Medical Center, Box 111B, Milwaukee, WI 53295. FAX 414-383-8010.
Pharmacies, supermarkets, and health food stores sell fish oil capsules for prevention of cardiovascular disease. Has this therapy proved effective? These 3 meta-analyses and 1 other (1) provide some answers. Gapinski and colleagues reported that fish oil was associated with a significant reduction in angiographically defined restenosis after angioplasty. The studies by Appel and Morris and their colleagues showed that fish oil was associated with small reductions in BP in persons with hypertension and hypercholesterolemia.
Before fish oil supplementation is recommended routinely for such disorders, several issues should be considered. As is often the case, the numbers of participants involved in the reported trials have been small and have represented very selected groups. Few women, nonwhites, elderly persons, and patients with comorbidities have been studied. The trials assessing BP have been short; few have lasted more than 3 months. Most studies have compared fish oil supplementation, rather than high fish diets, with placebo capsules.
The doses that have been associated with positive effects have been on the order of 3.5 to 5 grams daily. This is equivalent to 8 to 10 fish oil capsules that are available commercially. (This is roughly equivalent to the following numbers of 100-gram servings of fish daily: mackerel, 1 to 2; salmon, 3 to 4; tuna, 6 to 10; and flounder, 15 to 25 [2, 3].) It is unclear whether benefits can be achieved through supplementations with small amounts of commercially prepared fish oil.
It is also unclear whether high doses of fish oil (> 6 g/d) have detrimental effects, such as higher restenosis rates or major bleeding risks. Even doses of 4 to 5 grams daily may produce side effects, such as elevated low-density lipoprotein cholesterol, belching, bad taste, and diarrhea (3). It may be difficult to achieve high compliance with the prescription of a large number of pills that are associated with socially undesirable side effects. Finally, the trials reviewed have assessed physiologic or intermediate outcomes, such as angiographic lesions and BP, rather than the clinical outcomes of angina or myocardial infarction.
Looking at fish consumption, rather than fish oil supplementation, several prospective studies and 1 randomized controlled trial have suggested that modest dietary fatty fish consumption is associated with decreases in all-cause and ischemic heart disease mortality (4, 5). The randomized trial evaluated 3 dietary interventions (low fat, high fatty fish, and high fiber) in 2033 men with recent myocardial infarction (5). The fatty fish diet consisted of at least 2 weekly portions of fish such as mackerel, herring, or sardines. 22% of participants in the fatty fish group also took very low doses of fish oil supplementation. The rate of all-cause mortality among the men on the fish diet decreased significantly from 12.8% to 9.3% (relative risk reduction, 29%). Ischemic heart disease mortality also fell significantly from 11.4% to 7.7% (relative risk reduction, 33%). No clinically significant side effects were seen with the fish diet, and serum cholesterol was not significantly increased at the end of the 2-year trial.
Although these 3 well-designed meta-analyses show that fish oil supplementation lowers BP in patients with hypertension and that it prevents restenosis after angioplasty, it is premature to adopt fish oil supplementation as routine clinical practice for several reasons. The information available may not be generalizable to most patients. The therapeutic window for fish oil is not well defined, and side effects occur. The long-term clinical outcomes are unknown. Finally, the feasibility of achieving compliance with multiple pills without adversely affecting compliance with other clinically proved regimens (e.g., diuretics for hypertension) is not clear.
Despite these deficiencies in our knowledge regarding fish oil supplementation, current findings are promising. Clinicians should look for results of ongoing multicenter trials that will better establish the safety, tolerability, and efficacy of palatable doses of fish oils. Whether fish oil supplementation is superior to dietary fish intake should also be evaluated. Meanwhile, it is prudent to routinely recommend modest dietary intake of fatty fish, especially for persons who have had a myocardial infarction.
Cynthia D. Mulrow, MD
Audie L. Murphy Memorial Veterans Hospital San Antonio, Texas, USA