n-3 Polyunsaturated Fatty Acids and Atrial Fibrillation in Patients With Chronic Heart Failure

The GISSI-HF Trial

Aneta Aleksova; Serge Masson; Aldo P. Maggioni; Donata Lucci; Gianna Fabbri; Luciano Beretta; Lucio Mos; Anna Maria Paino; Gian Luigi Nicolosi; Roberto Marchioli; Gianni Tognoni; Luigi Tavazzi; Gianfranco Sinagra; Roberto Latini


Eur J Heart Fail. 2013;15(11):1289-1295. 

In This Article

Abstract and Introduction


Aims In the last few years, n-3 polyunsaturated acids (PUFAs) have been extensively studied for the prevention of AF, mostly in patients without heart failure (HF) or LV dysfunction. This post-hoc analysis of the GISSI-HF trial assessed the effect of n-3 PUFAs on AF in patients with chronic HF without AF at study entry over a median follow-up of 3.9 years.

Methods and results In the GISSI-HF trial, 6975 patients with chronic HF were randomized to 1 g daily of n-3 PUFAs or placebo on top of recommended therapy for HF. Of these, 1140 (16.3%) had AF at baseline ECG and were excluded from the present analysis. AF during the trial was defined as the presence of AF on the ECGs done at each visit during the trial or AF as a cause of worsening HF or hospital admission or as an event during hospitalization. Dietary fish consumption and the circulating levels of n-3 PUFAs (the latter in a subset of 1203 patients) were also available. Among the 5835 patients without AF at study entry, 444 randomized to n-3 PUFAs (15.2%) and 408 to placebo (14.0%) developed AF (unadjusted hazard 1.10, P = 0.19). Lower circulating n-3 PUFA levels were independently associated with higher AF prevalence at study entry, but not with its new occurrence.

Conclusions Despite an inverse relationship between plasma n-3 PUFA levels and prevalent AF, this study found no evidence that 1 g daily n-3 PUFA supplementation in patients with chronic HF reduces incident AF.


Atrial fibrillation places a large burden on society, affecting 1–2% of the population, and its prevalence is expected to rise considerably by 2050.[1] Structural and electric remodelling and dysfunction of the atria facilitate the initiation and maintenance of this arrhythmia.[2] Prevention of AF may be the preferable strategy, but prevention depends on identifying and correcting risk factors that favour the onset of AF. The Framingham Heart Study showed that age, male sex, body mass index, hypertension, heart failure (HF), and valvular diseases were independent risk factors for AF.[3,4] Atrial fibrillation is the most frequent sustained arrhythmia in patients with HF, with a prevalence depending of the severity of HF,[5–9] and its importance has been evidenced by the latest European Society of Cardiology guidelines on HF.[10] In view of the loss of heart rate control and the propensity for thrombogenesis, AF is associated with a risk of thrombo-embolism, impaired quality of life, frequent hospital admissions, and increased mortality rates.[2] The conventional therapies—antiarrhythmic drugs and/or cardioversion—can often restore sinus rhythm, but relapses are very frequent.[1] New therapeutic strategies are urgently needed.

n-3 polyunsaturated fatty acids (n-3 PUFAs), acting in prevention of atrial remodelling, may slow the development of AF,[11] but some studies show protection[12,13] and others no effect[14–16] on AF development or recurrence.

No previous studies analysed the role of n-3 PUFA supplementation on AF prevention in patients with chronic HF. The present post-hoc analysis of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca (GISSI-HF) trial examined the effect of n-3 PUFA supplementation on new episodes of AF in 5835 patients with chronic HF, without AF at randomization.