HRS: Omega-3 to prevent post-CABG a-fib provides FISH-y results
DENVER-Administering omega-3 polyunsaturated fatty acids prior to CABG surgery had no clinical benefit for the prevention of post-CABG surgery atrial fibrillation (AF), even though prior studies have found that increasing dose or administering the oil in an injection could be beneficial, according to a late-breaking clinical trial presented this morning at the 31st annual Heart Rhythm Society scientific sessions.
Lead author Chirag M. Sandesara, MD, of the Virginia Cardiovascular Associates in Manassas, Va., said that the FISH (fatty acids to inhibit superventricular arrhythmias after cardiac surgery) trial is the largest trial to study the effect omega-3 fatty acids have on the prevention of AF.
“AF after CABG surgery remains a major health problem,” said Sandesara. “Incidents range from 20 to 50 percent and it affects morbidity, increases hospital length of stay and occurs more commonly in the elderly population.”
To off-set these risks, Sandesara said that prior studies have shown there are possible mechanisms in omega-3 fatty acids that may reduce arrhythmia by providing the ability to block ion channels.
Resent trials conducted to evaluate the potential fish oil may have in its ability to decrease rates of AF showed contradictory results.
While one clinical trial proved that the administration of omega-3 fatty acids reduced patient length of stay and created patient benefit to decrease AF, most showed no differentiations in AF outcomes after CABG surgery.
Only one German/Swedish study showed that patients reaped the benefits of omega-3 fatty acids when they were administered an intravenous dose of 100 mg of omega-3, combined with other substitutes, at the time of surgery and throughout the hospital stay, post-CABG, said Sandesara.
The FISH trial, a randomized, double-blind, placebo-controlled trial took place at 10 centers throughout the U.S., and enrolled 260 patients between the ages of 18 and 85 years old who were undergoing CABG or concomitant valve surgery.
During the study, patients were randomized at a 1:1 ratio to receive either perioperative high-grade, purified FDA approved omega-3 oil (n=130) or a placebo (n=130) laced with omega-6 oil.
Each of the 1 mg doses of omega-3 included 465 mg of eicosapentaenoic acid (EPA) and 357 mg of docosahexaenoic acid (DHA).
The patients in the omega-3 arm were administered two grams orally twice a day until the day of CABG surgery and continued to receive the drug or placebo until the primary endpoint—reducing post-op AF— was reached, or 14 days, whichever came first, said Sandesara.
Results showed that there were no significant differences in the outcomes between either patient cohorts. Rates of these outcomes were 30 percent in the omega-3 arm compared to 33 percent in the placebo arm.
“Notably, patients that were in either the fish oil or the placebo group had a similar incidence of post-CABG AF, between 28-30 percent.”
Additionally, Sandesara said that there were also no significant differences in length of stay, MI, stroke, bleeding or recurrence of AF or rehospitalization rates for AF in either study arms.
During the study, the researchers also measured the tissue levels and the plasma fatty acid levels. According to Sandesara, results of these tests found a significant increase in EPA and DHA levels, from 2.78 to 4.35.
According to Sandesara, these rather insignificant results may be due to the high levels of omega-6 fatty acids placed in the placebo. “Because the Western diet is very high in omega-6 fatty acids, compared to the Mediterranean diet, which is very high in omega-3 fatty acids.”
Sandesara attributed this factor to why the intravenous dose of omega-3 fatty acids worked in the previous study conducted overseas.
Another problem, said Sandesara, is the fact that no prior data exist that show what the effective dose of omega-3 should be prior to CABG surgery.
“What we do know is that in patients that might require a higher level, we may have to off-set the omega-6 level to get enough omega-3 in their bloodstream to overcome the issue.”
He said that reducing AF could decrease once the dose-response relationship is figured out.
“The issue though that becomes important to address here is if that’s the amount that we have in our plasma, how much is actually getting into our cellular lipid pools, and that’s what we don’t know,” said Sandesara.
Sandesara said that patients may need more fish oil, besides what’s already in the plasma to create cellular pools that may actually show a positive anti-arrhythmic effect.
While omega-3 has been linked and associated with decreasing cardiovascular mortality, Sandesara said a clinical benefit of decreased rates of atrial arrhythmia was not found.
“Omega-3 had a significant effect on plasma EPA/DHA levels, but did not reduce the incidence of post CABG-AF,” Sandesara concluded.
Lead author Chirag M. Sandesara, MD, of the Virginia Cardiovascular Associates in Manassas, Va., said that the FISH (fatty acids to inhibit superventricular arrhythmias after cardiac surgery) trial is the largest trial to study the effect omega-3 fatty acids have on the prevention of AF.
“AF after CABG surgery remains a major health problem,” said Sandesara. “Incidents range from 20 to 50 percent and it affects morbidity, increases hospital length of stay and occurs more commonly in the elderly population.”
To off-set these risks, Sandesara said that prior studies have shown there are possible mechanisms in omega-3 fatty acids that may reduce arrhythmia by providing the ability to block ion channels.
Resent trials conducted to evaluate the potential fish oil may have in its ability to decrease rates of AF showed contradictory results.
While one clinical trial proved that the administration of omega-3 fatty acids reduced patient length of stay and created patient benefit to decrease AF, most showed no differentiations in AF outcomes after CABG surgery.
Only one German/Swedish study showed that patients reaped the benefits of omega-3 fatty acids when they were administered an intravenous dose of 100 mg of omega-3, combined with other substitutes, at the time of surgery and throughout the hospital stay, post-CABG, said Sandesara.
The FISH trial, a randomized, double-blind, placebo-controlled trial took place at 10 centers throughout the U.S., and enrolled 260 patients between the ages of 18 and 85 years old who were undergoing CABG or concomitant valve surgery.
During the study, patients were randomized at a 1:1 ratio to receive either perioperative high-grade, purified FDA approved omega-3 oil (n=130) or a placebo (n=130) laced with omega-6 oil.
Each of the 1 mg doses of omega-3 included 465 mg of eicosapentaenoic acid (EPA) and 357 mg of docosahexaenoic acid (DHA).
The patients in the omega-3 arm were administered two grams orally twice a day until the day of CABG surgery and continued to receive the drug or placebo until the primary endpoint—reducing post-op AF— was reached, or 14 days, whichever came first, said Sandesara.
Results showed that there were no significant differences in the outcomes between either patient cohorts. Rates of these outcomes were 30 percent in the omega-3 arm compared to 33 percent in the placebo arm.
“Notably, patients that were in either the fish oil or the placebo group had a similar incidence of post-CABG AF, between 28-30 percent.”
Additionally, Sandesara said that there were also no significant differences in length of stay, MI, stroke, bleeding or recurrence of AF or rehospitalization rates for AF in either study arms.
During the study, the researchers also measured the tissue levels and the plasma fatty acid levels. According to Sandesara, results of these tests found a significant increase in EPA and DHA levels, from 2.78 to 4.35.
According to Sandesara, these rather insignificant results may be due to the high levels of omega-6 fatty acids placed in the placebo. “Because the Western diet is very high in omega-6 fatty acids, compared to the Mediterranean diet, which is very high in omega-3 fatty acids.”
Sandesara attributed this factor to why the intravenous dose of omega-3 fatty acids worked in the previous study conducted overseas.
Another problem, said Sandesara, is the fact that no prior data exist that show what the effective dose of omega-3 should be prior to CABG surgery.
“What we do know is that in patients that might require a higher level, we may have to off-set the omega-6 level to get enough omega-3 in their bloodstream to overcome the issue.”
He said that reducing AF could decrease once the dose-response relationship is figured out.
“The issue though that becomes important to address here is if that’s the amount that we have in our plasma, how much is actually getting into our cellular lipid pools, and that’s what we don’t know,” said Sandesara.
Sandesara said that patients may need more fish oil, besides what’s already in the plasma to create cellular pools that may actually show a positive anti-arrhythmic effect.
While omega-3 has been linked and associated with decreasing cardiovascular mortality, Sandesara said a clinical benefit of decreased rates of atrial arrhythmia was not found.
“Omega-3 had a significant effect on plasma EPA/DHA levels, but did not reduce the incidence of post CABG-AF,” Sandesara concluded.