Fish-Oil Caps Don't Stop Post-CABG Atrial Fib in Randomized Trial

May 17, 2010

May 17, 2010 (Denver, Colorado) — Patients scheduled for coronary bypass surgery who start taking fish-oil capsules a few days before the procedure and stay on them for at least a few weeks aren't protected against clinically significant post-CABG atrial fibrillation (AF), nor do they spend less time in the hospital or have fewer clinical complications, according to a randomized placebo-controlled study reported here at the Heart Rhythm Society (HRS) 2010 Scientific Sessions.

The results of the "largest multicenter study to date" to address whether oral intake of omega-3 polyunsaturated fatty acids (PUFAs) in fish oil can suppress post-CABG AF are consistent with most previous such studies in suggesting that there's no effect, according to lead author Dr Chirag Sandesara (Virginia Cardiovascular Associates, Manassas), who presented the study.

The trial, conducted at 10 US centers, was unusual among its peers, he said, in using the capsules containing "purified" fish oil (Lovaza, GlaxoSmithKline), which are FDA-approved for the treatment of hypertriglyceridemia.

They were given at the same dosage approved for that indication, two 1-g capsules twice daily, starting at least 24 hours before surgery. Each capsule contains about 465 mg eicosapentaenoic acid (EPA) and 375 mg docosahexaenoic acid (DHA).

At a press conference, Sandesara told reporters that the doses used are a "potential limitation" of the trial, because patients generally started taking the capsules only a matter of days before surgery. Because it was conducted at large, high-CABG-volume centers, there was "a very short time between the cardiovascular clinic visit and the day of surgery; thus, we were actually quite limited in the amount of fish oil that could be given." But they all took at least 6 g of omega-3 PUFAs before surgery.

The trial's 260 patients undergoing CABG with or without valve surgery were evenly randomized in a double-blind fashion to receive the fish-oil caps or a matched placebo containing omega-6-rich corn oil. Patients taking antiarrhythmic drugs with persistent AF, or with unstable angina or heart failure, were excluded.

Ten patients in the fish-oil group and seven in the control group were dropped from the analysis because they ultimately didn't undergo surgery, leaving 120 and 123 patients, respectively. Another five and four patients, respectively, never completed the full study but were included in the analysis. The randomization groups were similar with respect to sex, age, ejection fraction, left atrial size, and prevalence of renal failure, hypertension, MI, heart failure, and diabetes.

At the time of surgery and four days later, those taking fish-oil caps showed significantly higher plasma levels of omega-3 PUFAs and a drop in the ratio of omega-6 to omega-3 PUFAs than those taking the placebo caps (p<0.0001 for both differences).

At two weeks, there was no significant difference between the groups in rate of the primary end point, which was documented, clinically significant post-op AF or atrial flutter requiring treatment (30% for the omega-3 group and 33% for the controls; p=0.67). Nor were there significant differences in prespecified secondary end points, including post-op length of hospital stay; rehospitalization for AF; rate of perioperative MI; stroke, bleeding, or heart failure; or "life threatening or sustained" ventricular arrhythmias.

Sandesara told heartwire that there was "robust use of beta blockers and statins" in the study; about 80% of patients in both groups were taking the former and about 74% of both groups were taking the latter. Both drug classes are known to influence AF. It's possible, he said, that their extensive use made it harder for the fish-oil therapy to show a protective effect.

Although some evidence suggests that plasma levels of omega-3 PUFAs reach a stable level within 24 to 48 hours, he said, how much fish oil it takes to usefully affect the heart's electrical system is not known. "Perhaps we need even more fish oil, besides what's already in the plasma, to actually get to the cellular pools, to block ion channels [or] modulate gap junctions, potentially reducing arrhythmias."

Favorable Atrial Electrical Remodeling From Omega-3 PUFAs

Although there have been mixed results from studies looking at whether taking omega-3 PUFAs in fish oil can suppress arrhythmias or prevent sudden death, there is abundant laboratory and animal data to support such an effect. In a randomized mechanistic study conducted in patients without structural heart disease who underwent electrophysiologic (EP) testing for suspected supraventricular tachycardia, presented here at the HRS sessions, those that took fish-oil caps at 2 g/day for at least a month showed a drop in AF inducibility and other EP evidence of reduced vulnerability to AF.

The 50 patients were randomized to receive fish-oil capsules at 2 g/day or standard therapy only, starting a minimum of 30 days and an average of 60 days prior to EP testing. The two groups were similar with respect to age, duration of symptoms, LVEF, and LV and LA dimensions.

The capsules (Nu-Mega) contained omega-3 PUFAs from tuna oil, a form that is commonly used in Australia where the study was conducted, first author Dr Saurabh Kumar (Royal Melbourne Hospital, Parkville, Australia) told heartwire .

At the time of EP testing, EPA and DHA levels were significantly higher in those taking the fish oil (p<0.001 for both). The testing showed a mean AF cycle length of 202 ms in the 25 patients in the fish-oil group and 186 ms in the 25 patients in the control group (p=0.014). The fish-oil group also showed significant improvements in refractoriness at all pacing-cycle lengths at the distal coronary sinus (p<0.003) and proximal coronary sinus (p<0.001), increased refractoriness at the high right atrium (p<0.004), and less conduction delay within the coronary sinus (p<0.004).

The fish-oil group showed an 89% reduction in the rate of inducible AF lasting at least 30 seconds (p=0.009). Inducibility of AF was independently related to serum DHA levels (odds ratio, 0.37; 95% CI, 0.14-0.99; p=0.049) but not to levels of EPA.

Sandesarra and his coauthors report financial relationships with GlaxoSmithKline, which funded the study. The study from Kumar was partly funded by Pfizer; Nu-Mega supplied the fish-oil capsules but provided no other sponsorship, he said.

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