Large clinical trial shows benefits of Omega-3 in patients with Chronic Heart Failure

Good news: taking daily omega-3 fatty acids supplements (n-3 polyunsaturated fatty acids or PUFAs) may improve survival prospects and reduce mortality among patients with chronic heart failure (HF).

This is one of the unexpected outcomes from a large scale Italian study (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico Heart Failure or GISSI-HF study) involving 6,975 patients with New York Heart Association (NYHA) class II-IV HF of any cause and with any left ventricular ejection fraction who were randomized to receive daily supplementation of omega-3 fatty acids 1 g (805-882 mg eicosapentaenoic acid and docosahexaenoic acid in the average ratio 1:1.2) or placebo. In addition, 4,574 patients of the same group were also randomized to receive Crestor, (rosuvastatin calcium, 10 mg daily, Astra Zeneca) or placebo.

Trial design
The GISSI-HF trial was designed to investigate the effects of omega-3 fatty acids and statin therapy on mortality and morbidity in patients with chronic heart failure (HF).

Trial results
The results of this trial, boosting the health-giving reputation of omega-3 fatty acids fish oil supplementation, were presented by dr Luigi Tavazzi of the Fondazione Policlinico San Matteo, Pavia in Italy, during the European Society of Cardiology (ESC) Congress 2008 in Munich, Germany and simultaneously published in The Lancet (1,2).

The investigators conducting the trial were especially glad to report positive results for patients with chronic heart failure (HF), an exceptionally difficult to treat condition in which the heart struggles to pump blood effectively, which causes shortness of breath and other serious problems. They found that supplementation with omega-3 fatty acids greatly benefitted this group of patients.

Patients were followed for almost four years (average 3.9 years). The supplementation with omega-3 fatty acids resulted in a 1.8% absolute risk reduction, which translated into a 9% reduction of mortality. The results also show a 2.3% absolute reduction in all-cause death or hospital admission for cardiovascular reasons, which translated in an 8% reduction of admission to the hospital for cardiovascular causes.

‘Real world meaning’
Translating these percentages to ‘real world meaning’, the chairperson of the GISSI-HF steering committee, dr. Tavazzi, explained that the absolute risk reductions achieved with omega-3 means that 56 patients would need to be treated over a 4-year period to prevent one death, while 44 would need to be treated to avoid a death or a hospital admission for cardiovascular causes.

In his conclusion he said that ‘Although this moderate benefit was smaller than expected, we should note that it was obtained in a population already treated with various recommended therapies, was consistent across all the predefined subgroups, and was further supported by the findings of the per-protocol analysis.’

Benefits after 2 year
An interesting aspect of the study is that the benefits of supplementation with omega-3 fatty acids only became clear after about 2 years of treatment. Commenting on this remarkable aspect, dr Michel Komajda of the Pitie Salpetriere Hospital and the Université Pierre et Marie Curie, in Paris, France, one of the other investigators in this trial, explained that ‘Mortality curves for treated and placebo groups only started to diverge after two years of follow-up’.

He further explained that while current European and U.S. treatment guidelines focus on the role of omega-3 in preventing heart disease wider guidance to include treating heart failure could be warranted.’ The benefit was statistically significant and at present physicians have little further to offer patients with heart failure. Therefore, I am sure that those of us who have responsibility for drawing up the next CHF guidelines will pay a lot of attention to the results of this trial.’

This sentiment was echoed by dr Gregg Fonarow of the of the Ahmanson-UCLA (University of California) Cardiomyopathy Center in Los Angeles, USA. In an editorial in The Lancet (3) dr Fonarow stated that despite the fact that ‘many questions remain about the mechanism of action, optimum dosing, and formulation, supplementation with n-3 polyunsaturated fatty acids (omega-3 fatty acids) should join the short list of evidence-based life-prolonging therapies for heart failure (HF).’

Clear benefits of omega-3 fatty acids
Omega-3 fatty acids have in the past been linked to a range of health benefits, including reducing the risk of heart attacks, strokes, Alzheimer's disease and depression. One explanation is that omega-3 fatty acids are thought to help by stabilizing the electrical signals of the heart, as well as reducing blood fat levels. Furthermore, researchers believe that omega-3 fatty acids could possibly exert favorable effects on inflammatory processes, such as reductions in endothelial activation and cytokine production, as well as influence platelet aggregation, blood pressure, heart rate, ventricular function, and autonomic tone.

The advantage of omega-3 fatty acids supplementation is that it is cheap, well-tolerated and does not interfere with other medications, making it an attractive option for patients with chronic heart failure (HF) even if the clinical benefits are relatively moderate. This advantage was confirmed by dr Tavazzi who spoke of an ‘Effective, safe, simple, and cheap’ treatment option.

Long term effects
The GISSI-HF study showed that long term treatment with low-dose omega-3 fatty acids was associated with a significant reduction of total mortality of 21% in patients who survived a recent myocardial infarct (starting treatment within 3 months from symptom onset). The analysis of the causes of death showed that, among all cardiac causes, the most affected by omega-3 fatty acids was sudden cardiac death. Other experimental, epidemiological, as well as small size human studies confirm these findings and support the hypothesis that omega-3fatty acids can exert antiarrhythmic or antifibrillatory effects.This conclusion can be relevant for heart failure patients because nearly half of the deaths of patients with chronic heart failure (HR) are classified as sudden cardiac deaths. Analysis of the trial data showed that in patients with left ventricular dysfunction or heart failure enrolled in the trial, the effects of omega-3 fatty acids on all-cause and sudden mortality were similar to those observed in the total population of the trial.

The researchers believe that findings of this study should also be taken as a message to the public to eat more fish to keep their hearts healthy.

Official study title: A Large Scale Clinical Trial Testing the Effects of n-3 PUFA and Rosuvastatin on Mortality-Morbidity of Patients With Symptomatic Congestive Heart Failure

For more information about omega-3 fatty acids, visit Vitaelin Nutraceuticals at http://vitaelinhealthcenter.com/

Sources

1. 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. Available online at: http://www.thelancet.com.
2. 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. Available online at: http://www.thelancet.com.
3. Fonarow GC. Statins and n-3 fatty acid supplementation in heart failure. Lancet 2008; DOI: 10.1016/S0140-6736(08)61239-8. Available online at: http://www.thelancet.com.
4. Kjekhus J, Apetrei E, Barrios V, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med 2007; DOI: 10.1056.nejmoa0706201. Available online at: http://www.nejm.org
5. Hjalmarson Å Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA)-Results of an outcomes trial in patients with ischemic heart disease and heart failure. American Heart Association 2007 Scientific Sessions; November 5, 2007; Orlando, FL, Late-breaking clinical trials 2.