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 -3 Fatty Acids for the Prevention of Atrial Fibrillation After Coronary Artery Bypass Surgery: A Randomized, Controlled Trial
Anh Hoang, PharmD and
Todd Canada, PharmD, BCNSP
Objectives: The aim of this study was to assess the efficacy of
preoperative and postoperative treatment with  -3 polyunsaturated fatty
acids (PUFAs) in preventing the occurrence of atrial fibrillation (AF) after
coronary artery bypass graft surgery (CABG). Background:
Postoperative AF is a common complication of CABG. There is growing clinical
evidence that PUFAs have cardiac antiarrhythmic effects. Methods: A
total of 160 patients were prospectively randomized to a control group (81
patients, 13 female, 64.9 ± 9.1 years) or PUFAs 2 g/day (79 patients,
11 female, 66.2 ± 8.0 years) for at least 5 days before elective CABG
and until the day of discharge from the hospital. The primary end point was
the development of AF in the postoperative period. The secondary end point was
the hospital length of stay after surgery. All end points were independently
adjudicated by 2 cardiologists blinded to treatment assignment.
Results: The clinical and surgical characteristics of the patients in
the 2 groups were similar. Postoperative AF developed in 27 patients of the
control group (33.3%) and in 12 patients of the PUFAs group (15.2%)
(p = .013). There was no significant difference in the incidence of
nonfatal postoperative complications, and postoperative mortality was similar
in the PUFAs-treated patients (1.3%) vs controls (2.5%). After CABG,
the PUFAs patients were hospitalized for significantly fewer days than
controls (7.3 ± 2.1 days vs 8.2 ± 2.6 days, p
= .017). Conclusions: This study first demonstrates that PUFA
administration during hospitalization in patients undergoing CABG
substantially reduced the incidence of postoperative AF (54.4%) and was
associated with a shorter hospital stay. (J Am Coll Cardiol.
2005;45:1723–1728.)
COMMENT: Postoperative AF occurs in 25%–40% of patients
undergoing open heart surgery and is associated with increased length of
hospital stay and costs. Previous experimental and clinical studies have
suggested that the use of PUFAs may prevent cardiac arrhythmias and sudden
death.1 There is
some evidence from experimental studies that PUFAs have antiarrhythmic effects
on the atrial muscle as well. The purpose of this study was to determine
whether preoperative and postoperative treatment with PUFAs was safe and
effective in the prevention of AF during the hospitalization period after
CABG.
This was an open-label, prospective, randomized, controlled trial with
parallel groups conducted over a period of 18 months at a single institution
in Rome, Italy. Patients referred to the institution for elective cardiac
surgery were recruited for enrollment and included if they were >18 years
of age, were in normal sinus rhythm, and had stable hemodynamics before
surgery. Excluded patients were those who needed concomitant valvular surgery,
had a history of supraventricular arrhythmias, or were currently using
antiarrhythmic medications other than β-blockers, calcium-channel
blockers, or digitalis. Patients were randomized to usual care (control group)
or usual care plus PUFAs (treatment group). The dose of PUFAs was 2 oral
capsules per day, started a minimum of 5 days prior to surgery. The 2 capsules
of PUFAs contained 850–882 mg eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA) as ethyl esters in the average ratio of EPA/DHA 1:2
(commercially available from Societa Prodotti Antibiotici, Milan, Italy).
Treatment was continued via a nasogastric tube postsurgery
(24–36 hours), then orally until hospital discharge. Compliance with
treatment was monitored by pill count and was 98%. The primary end point was
the incidence of postoperative AF as detected by continuous
electrocardiography for the first 4–5 days postoperatively, then with a
daily electrocardiogram until hospital discharge. The authors anticipated a
15% reduction in the occurrence of postoperative AF with PUFAs compared with
controls, and this helped determine their sample size.
By the third interim analysis at 18 months, 160 patients were enrolled. At
this time, enrollment was terminated early as a result of a significant effect
in favor of the PUFAs group (compared with controls). The study population was
composed of mainly elderly men (85% male, mean age of 65 years) with systemic
hypertension (80%) and previous myocardial infarction (52.5%). Perioperative
β-blockers and calcium-channel blockers were used in 58.2% and 27.8% of
patients in the PUFAs group compared with 56.8% and 30.9% in the control
group, respectively. A statistically and clinically significant decrease in
the primary end point was seen. The rate of postoperative AF was 15.2% in the
PUFAs group compared with 33.3% in the control group (odds ratio [OR], 0.35;
p = .013). There was no difference in the time to onset of AF between
the 2 groups. The mean duration of AF was not significantly different: 15.5
hours in PUFAs patients compared with 23.9 hours in control patients
(p = .125). Age and use of PUFAS were noted to be independent
predictors of postoperative AF. The study did not find any influence of
β-blocker use on the prevalence of AF in either patient group. The
secondary end point, length of hospital stay, was also found to be reduced by
0.9 days (7.3 days in the PUFAs group vs 8.2 days in the control
group; p = .017); however, it is not clear if this was clinically
significant. There was no difference observed for in-hospital morbidity or
mortality. However, 1 patient in the PUFAs group developed an allergic skin
rash on the first day of treatment and required discontinuation of the
supplement.
Previous studies have shown that PUFAs reduced the risk of sudden death and
ventricular
arrhythmias.1
Interestingly, 2 recent prospective, cohort studies reported conflicting
findings with regards to
AF.2,3
One study found that the consumption of -3 fatty acids from fish
consumption was associated with a reduction in risk of AF, but the other study
did not. The current study, therefore, represents the first randomized
clinical trial to show that PUFAs are effective at preventing AF after CABG in
selected patients. The incidence of AF in the control group was 33.3%, which
is similar to that reported in the literature. The reduction in the incidence
of postoperative AF (OR, 0.35) was also of similar magnitude to other
pharmacologic alternatives, such as β-blockers (OR, 0.39), sotalol (OR,
0.35), and amiodarone (OR, 0.48), as reported in a 2002
meta-analysis.4 One
of the limitations of this study was that it was not blinded. However, 2
cardiologists, who were blinded, performed the adjudication of the primary and
secondary end points. Furthermore, the results of this study are limited to
patients with no prior history of AF undergoing elective CABG. It would be
interesting to determine whether higher-risk patients (ie, those with a
history of AF and those undergoing valvular surgery) would also benefit from
PUFA supplementation. Nevertheless, the positive results of this study are
encouraging. Further trials are warranted in order to validate these exciting
findings.
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Contributing Editor—Todd Canada, PharmD, BCNSP
University of Texas MD Anderson Cancer Center, Houston, Texas
Calo L, Bianconi L, Colivicchi F, et a1
Department of Cardiac Diseases, San Filippo Neri Hospital, Rome,
Italy
- Marchioli R, Barzi F, Bomba E, et al. 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; 105:1897
–1903.[Abstract/Free Full Text]
- Mozaffarian D, Psaty BM, Rimm EB, et al. Fish intake and risk of
incident atrial fibrillation. Circulation.2004; 110:368
–373.[Abstract/Free Full Text]
- Frost L, Vestergaard P. n-3 Fatty acids consumed from fish and risk
of atrial fibrillation or flutter: the Danish Diet, Cancer, and Health Study.
Am J Clin Nutr.2005; 81:50
–54.[Abstract/Free Full Text]
- Crystal E, Connolly SJ, Sleik K, Ginger TJ, Yusuf S. Interventions
on prevention of postoperative atrial fibrillation in patients undergoing
heart surgery: a meta-analysis. Circulation.2002; 106:75
–80.[Abstract/Free Full Text]
Nutrition in Clinical Practice, Vol. 21, No. 2,
189-190 (2006)
DOI: 10.1177/0115426506021002189
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