Daily dose of omega-3s reduces hospital-admission and death rates modestly among people diagnosed with chronic heart failure; statin drug shows no benefits 09/01/2008
- Fish oil cut death risk by 8% among people with congestive heart failure (CHF), in large clinical trial.
- No risk reductions were seen among CHF patients taking the common statin drug Crestor (rosuvastatin).
- Results affirm the promise of omega-3s for protecting overall cardiovascular health
- To help prevent strokes and cardiovascular disease in healthy people.
- To reduce the risk of stroke, sudden death, or a second heart attack among patients diagnosed with cardiovascular disease.
Dr. Leaf also cited other studies, which indicate that supplemental fish oil sharply reduces the risk of fatal cardiac arrhythmias among recent heart attack victims and among people with implanted cardiac defibrillators at high risk for fatal ventricular arrhythmias.
As Dr. Leaf wrote, “These studies demonstrate that fish oil fatty acids have beneficial effects on coronary heart disease” (Leaf A 2008).
New trial adds congestive heart failure to list of omega-3 benefits
The authors of the new study recruited 6,975 people diagnosed with chronic heart failure and randomly assigned them to take either 1 gram of omega-3s (contained in fish oil capsules) daily or placebo capsules (GISSI-HF 2008).
Chronic heart failure (CHF) is a life-threatening condition in which the heart can no longer pump enough blood to the rest of the body.
After nearly four years, people in the fish oil group were 8 percent less likely to have been admitted to hospital or to have died, compared with the members of the placebo group.
In both groups, stomach upset was the most frequent adverse reaction, occurring in three percent of participants.
As the authors wrote, “Our study shows that the long-term administration of 1 gram per day of omega-3 [fatty acids] was effective in reducing both all-cause mortality [death] and admissions to hospital for cardiovascular reasons” (GISSI-HF 2008).
Statins show no benefit in companion clinical trial
The same authors conducted a second clinical trial to test the effects of a common cholesterol-lowering statin drug – Crestor (rosuvastatin) – in patients with heart failure (GISSI-HF 2008).
The rationale for this trial was that statins exert anti-inflammatory effects, and it's believed that heart failure patients respond to measures that reduce certain aspects of inflammation.
The authors recruited 4,574 people diagnosed with chronic heart failure (CHF) and randomly assigned them to take either 10 mg of rosuvastatin daily or placebo pills.
After nearly four years, 657 patients (29 percent) had died from any cause in the rosuvastatin group, compared with 644 (28 percent) in the placebo group.
The proportions of patients who died or were admitted to hospital for cardiovascular causes were also similar in both groups.
As the authors concluded, “Rosuvastatin 10 mg daily did not affect clinical outcomes in patients with chronic heart failure of any cause …” (GISSI-HF 2008)
In other words, this particular statin drug produced no benefits in chronic heart failure patients.
In an accompanying comment, Dr. Gregg Fonarow of the UCLA Cardiomyopathy Center wrote, “For omega-3 fatty acid supplementation, benefits observed in other populations apply to patients with heart failure. For statins, the benefits, unfortunately, seem not to … every effort should be made to apply those therapies which are evidence-based to all eligible patients with heart failure.” (MNT 2008)
He's saying that when you follow the evidence, it makes sense for people with heart failure to consume ample omega-3s.
Interestingly, the trial was partially funded by two companies that make leading statin drugs – Pfizer (Lipitor) and AstraZeneca (Crestor) – whose managers could not have been pleased.
Omega-3s and heart failure: History and rationale
Compared with prevention of cardiovascular disease and its adverse effects (heart attack, arrhythmia, and stroke) there's been much less study of the effect of omega-3s in people with chronic heart failure, which is also called congestive heart failure (also CHF).
CHF usually develops over time and becomes a chronic, long-term condition, but it can also develop quickly.
The most common causes of CHF are hypertension (high blood pressure) and coronary artery disease, which reduces blood flow to the heart and thereby damages or kills heart-muscle cells needed to pump blood.
A 1998 study in dogs, conducted at the Tufts School of Veterinary Medicine, revealed that omega-3 fish oil supplements lowered levels of a key inflammatory marker linked to heart risks, improved appetite, led to weight gain, and improved the canines' heart function (Freeman LM et al. 1998; see “Heart-Sick Dogs Helped by Fish Oil”).
In 2006, university researchers from Maryland and New Orleans published the results of a small, placebo-controlled clinical trial in 14 patients with advanced chronic heart failure. The CHF patients on fish oil enjoyed two major benefits versus the placebo group (Mehra MR et al. 2006):
- They gained weight, thereby reversing the dangerous weight loss – called cardiac cachexia – that often occurs in advanced CHF.
- Blood levels of pro-inflammatory, cachexia-promoting immune-system chemicals (cytokines) dropped very substantially.
The pro-inflammatory cytokines suppressed by fish oil included TNF-alpha, elevated levels of which are risk factors for chronic heart failure and cardiac cachexia. (See “Fish Oil May Help Congestive Heart Failure Patients”.)
As the Maryland/New Orleans team wrote, “Fish oil therapy may represent a novel therapeutic approach in late-stage heart failure characterized by cardiac cachexia.” (Mehra MR et al. 2006)
- [No authors listed] Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet. 1999 Aug 7;354(9177):447-55. Erratum in: Lancet 2001 Feb 24;357(9256):642. Lancet. 2007 Jan 13;369(9556):106.
- Freeman LM, Rush JE, Kehayias JJ, Ross JN Jr, Meydani SN, Brown DJ, Dolnikowski GG, Marmor BN, White ME, Dinarello CA, Roubenoff R. Nutritional alterations and the effect of fish oil supplementation in dogs with heart failure. J Vet Intern Med. 1998 Nov-Dec;12(6):440-8
- GISSI-HF Investigators. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. The Lancet Early Online Publication, 31 August 2008. DOI:10.1016/S0140-6736(08)61239-8. Accessed online August 31, 2008 at http://www.thelancet.com/journals/lancet/article/PIIS0140673608612398/abstract?isEOP=true
- GISSI-HF Investigators. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. The Lancet Early Online Publication, 31 August 2008. DOI:10.1016/S0140-6736(08)61240-4. Accessed online August 31, 2008 at http://www.thelancet.com/journals/lancet/article/PIIS0140673608612404/abstract?isEOP=true
- Leaf A. Historical overview of n-3 fatty acids and coronary heart disease. Am J Clin Nutr. 2008 Jun;87(6):1978S-80S.
- Macchia A, Levantesi G, Franzosi MG, Geraci E, Maggioni AP, Marfisi R, Nicolosi GL, Schweiger C, Tavazzi L, Tognoni G, Valagussa F, Marchioli R; GISSI-Prevenzione Investigators. Left ventricular systolic dysfunction, total mortality, and sudden death in patients with myocardial infarction treated with n-3 polyunsaturated fatty acids. Eur J Heart Fail. 2005 Aug;7(5):904-9.
- Marchioli R, Barzi F, Bomba E, Chieffo C, Di Gregorio D, Di Mascio R, Franzosi MG, Geraci E, Levantesi G, Maggioni AP, Mantini L, Marfisi RM, Mastrogiuseppe G, Mininni N, Nicolosi GL, Santini M, Schweiger C, Tavazzi L, Tognoni G, Tucci C, Valagussa F; GISSI-Prevenzione Investigators. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation. 2002 Apr 23;105(16):1897-903.
- Marchioli R, Levantesi G, Macchia A, Maggioni AP, Marfisi RM, Silletta MG, Tavazzi L, Tognoni G, Valagussa F; GISSI-Prevenzione Investigators. Antiarrhythmic mechanisms of n-3 PUFA and the results of the GISSI-Prevenzione trial. J Membr Biol. 2005 Jul;206(2):117-28.
- Marchioli R, Schweiger C, Tavazzi L, Valagussa F. Efficacy of n-3 polyunsaturated fatty acids after myocardial infarction: results of GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico. Lipids. 2001;36 Suppl:S119-26.
- Medicalnewstoday.com (MNT). Omega-3 Polyunsaturated Fatty Acids Reduce Mortality And Hospital Admission In Patients With Heart Failure, Statins Show No Effect.
- 31 Aug 2008. Accessed online August 31, 2008 at http://www.medicalnewstoday.com/articles/119742.php
- Mehra MR, Lavie CJ, Ventura HO, Milani RV. Fish oils produce anti-inflammatory effects and improve body weight in severe heart failure. J Heart Lung Transplant. 2006 Jul;25(7):834-8. Epub 2006 May 24.
- Yndestad A, Damas JK, Oie E, Ueland T, Gullestad L, Aukrust P. Role of inflammation in the progression of heart failure. Curr Cardiol Rep. 2007 May;9(3):236-41. Review.