Omega-3 fatty acid supplements, but not statin drugs, can help patients with chronic heart failure, show two parallel studies conducted for the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico Heart Failure (GISSI-HF) trial and released for early online publication in the Lancet August 31, 2008.
Omega-3s’ positive outcomes are especially important since few effective options exist for patients with chronic heart failure.
In one study, Italian researchers gave 3,494 heart failure patients 1 gram/day of omega-3 fatty acids, while roughly the same number, (3,481), got a placebo. In the parallel study, the same team of Italian doctors gave 2,285 patients 10 mg daily of rosuvastatin (Crestor, AstraZeneca) and 2,289 patients a placebo.
After 3.9 years, omega-3 fatty acids had reduced all-cause mortality 9% and hospital admission for cardiovascular reasons (cardiovascular-induced death, nonfatal heart attack, or stroke) by 8%, while the statin drug produced no similar benefits.
Despite the fact that treatment with rosuvastatin lowered LDL cholesterol 27% at 3 years—down from 123 mg/dL at the beginning of the study to 90 mg/dL—the statin did not provide heart failure patients with the cardio-protective benefits delivered by omega-3 fatty acids.
Why might omega-3 fats help? Cell membranes, where key metabolic enzymes are embedded, are largely composed of fats. The higher the DHA content, the more flexible the cell membrane, and the more effectively enzymes can maneuver. EPA, which also concentrates in cell membranes, is the precursor of anti-inflammatory eicosanoids. Plus omega-3s have been shown to increase levels of HDL cholesterol and to stabilize heart cells’ electrical system, promoting a lower QTc interval and lessening the chance of arrhythmias. In contrast, statin drugs lower potentially harmful LDL cholesterol, which may not have much impact on heart failure.
While researchers were disappointed with statins’ failure to help heart failure patients, their response to omega-3s’ cardio-protective potential has been uniformly enthusiastic.
“This study changes the certainty of the evidence we have about fish oils,” said president of the American College of Cardiology, Dr. Douglas Weaver, who also noted that U.S. guidelines would likely change to recommend that heart patients eat more fish or take omega-3 fatty acid supplements. “This is a low-tech solution and could help all patients with cardiovascular problems,” said Weaver.
Chair of the GISSI-HF steering committee, Dr Luigi Tavazzi, presented the omega-3 data to the media during a European Society of Cardiology press conference, calling treatment with omega-3s an “effective, safe, simple, and cheap” option for patients with chronic heart failure. And in an editorial accompanying the two studies in the Lancet, Dr Gregg Fonarow at U.C.L.A seconded Tavassi, writing “…supplementation with n-3 polyunsaturated fatty acids should join the short list of evidence-based life-prolonging therapies for heart failure.”
Additional compelling evidence for omega-3s cardiovascular benefits comes from a June 2008 Mayo Clinic Proceedings review of 3 large controlled trials of 32,000 participants randomized to receive omega-3 supplements containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or placebo. These trials showed reductions in cardiovascular events of 19% to 45% in those given omega-3s.
Review authors noted that while target DHA and EPA consumption levels are about 1 gram/day for those with known coronary artery disease, and at least 500 mg/day for those without cardiovascular disease, patients with high triglycerides benefit from treatment with 3 to 4 grams/day of DHA and EPA, a dosage that lowers triglyceride levels by 20% to 50%.
They also emphasized that combination therapy with omega-3 fatty acids and a statin is a safe and effective way to improve lipid levels and cardiovascular prognosis beyond the benefits provided by statin therapy alone.
The July 2008 issue of the Journal of the American Dietetic Association notes one caveat: High intakes of omega-3s can cause excessive bleeding in some individuals. Patients taking more than 3 grams/day of EPA and DHA (the long chain omega-3 fatty acids) should do so only under a physician’s care. The US Food and Drug Administration has set the “generally regarded as safe” level for long-chain omega-3s at 3.0 g/day.
GISSI-HF investigators. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomized, double-blind, placebo-controlled trial. Lancet 2008. DOI: 10.1016/S0140-6736(08)61241-6. ↑
GISSI-HF investigators. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomized, double-blind, placebo-controlled trial. Lancet 2008. DOI: 10.1016/S0140-6736(08)61241-6. ↑
Fonarow GC. Statins and n-3 fatty acid supplementation in heart failure. Lancet 2008. DOI: 10.1016/S0140-6736(08)61239-8. ↑
Lee JH, O’Keefe JH, Lavie CJ, et al. Omega-3 fatty acids for cardioprotection. Mayo Clin Proc. 2008 Mar;83(3):324-32. ↑
Kris-Etherton PM, Hill AM. N-3 fatty acids: food or supplements?. J Am Diet Assoc. 2008 Jul;108(7):1125-30. ↑