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Dr. Nina B. Radford, MD, Cooper Clinic Cardiologist and Director of Clinical Research discusses the dose-related risk of atrial fibrillation with omega-3 fatty acid intake

Recent news reports suggest there may be a dose-related risk of atrial fibrillation with omega-3 fatty acid intake. Cooper Clinic Cardiologist and Director of Clinical Research Nina Radford, MD, explains the results of these recent medical studies and shares her view about how these results will affect her recommendations for patients.

Q: What is atrial fibrillation?

A: Atrial fibrillation (AFib) is the most common arrhythmia diagnosed in clinical practice. The American Heart Association estimates at least 2.7 million Americans are living with AFib. In addition, the Centers for Disease Control and Prevention (CDC) estimates 9% of adults over the age of 65 have AFib.

AFib is an irregular heart rhythm and occurs when the normal pacemaker function of the heart’s electrical system is overtaken by random impulses originating from multiple locations in the upper chambers of the heart. The development of AFib may be associated with a rapid heart rate (>150 bpm) in some patients while other patients may not notice any change in heart rate due to the use of certain medications or age-related changes in the heart’s electrical circuits that slow impulses down. AFib can come and go for minutes or hours at a time (paroxysmal), last for weeks at a time (persistent) or even become permanent.

The presence of AFib may be completely asymptomatic in some patients. Patients may become aware that they have AFib because it is detected by a smart watch or it may generate an error signal during home blood pressure monitoring. Conversely, some patients with AFib may have symptoms of palpitations, racing heart rate, reduced exercise tolerance or shortness of breath while at rest.

Q: Is AFib dangerous?

A: Because the upper chambers of the heart quiver or undulate with AFib, rather than beating forcefully in a regular rhythm, stasis of blood—associated with the development of blood clots—can occur in the nooks and crannies of the upper heart chambers (right and left atria). A blood clot can break free in the left atrium and travel through the neck arteries into the brain, causing a stroke.

The risk of stroke due to AFib is higher in patients who are older or have preexisting cardiovascular risk factors such as diabetes and hypertension. Patients who have cardiovascular conditions such as heart failure or vascular disease, prior heart attack or stroke and atherosclerosis in the leg arteries are also predisposed to having strokes. Females also are at greater risk than males. To reduce the risk of stroke in higher-risk patients, strong blood thinners are prescribed.

Q: How is AFib treated?

A: Treatment for AFib may include prescription blood thinners for high-risk patients or for any patient scheduled for a cardioversion─a procedure in which an electrical charge is used to restore normal heart rhythm. Some patients may receive medications designed for restoring or maintaining normal heart rhythms. Others may also undergo ablation, an invasive procedure to more permanently eliminate the rogue electrical signals in the upper heart chambers that cause AFib.

Q: Who is at risk for AFib?

A: The risk of developing AFib increases with age. The risk also increases with the presence of numerous clinical conditions, most of which can be prevented or treated, such as:

  • High blood pressure
  • Obesity
  • Diabetes
  • Heart disease including heart valve disorders, prior heart attack, heart failure and bouts of chest pain due to worsening coronary blockages
  • Excessive alcohol consumption
  • Smoking
  • Physical inactivity
  • Obstructive sleep apnea
  • Hyperthyroidism
  • Severe acute systemic illness such as pneumonia
  • Chronic respiratory diseases such as asthma

Finally, the risk of AFib is higher in middle-aged athletes who have participated in high-volume endurance activities for many years.

Q: Is there a correlation between omega-3 supplementation and AFib risk?

A: A correlation was shown in two recent clinical studies. In the REDUCE-It trial, 8,179 patients at high risk for cardiovascular disease were treated with 4 grams of omega-3 EPA daily or placebo. In the STRENGTH trial, another high-risk group of 13,086 patients were treated with 4 grams of omega-3 EPA and DHA daily versus placebo. After nearly five years, both treatment groups saw a significant increase in the risk of developing AFib. These trials included high-risk patients with established atherosclerotic cardiovascular disease, type 1 and 2 diabetes as well as those with elevated triglycerides on statin therapy. Risk factors also may have included a family history of premature artery disease, chronic smoking, elevated C-reactive protein, impaired kidney function, and coronary artery calcium levels greater than 300.

Cooper Complete Advanced Omega-3 contains 1.4 grams (1,400 mg) of EPA and DHA in each two-softgel daily serving. Therefore, it is important to note seven Advanced Omega-3 softgels are equivalent to the amount of omega-3 supplementation used in these trials.

Q: What does the research from the VITAL Rhythm Study show?

A: The VITAL Rhythm Study, otherwise known as the VITamin D and OmegA-3 TriaL, observed 25,871 individuals to determine if taking 50 mcg (2,000 IU) of vitamin D or 1 gram of omega-3 or both reduced the risk of cancer, heart disease and stroke. The investigators also analyzed the data from this trial to look at the development of AFib. In contrast to the studies discussed above, these participants were generally healthy and had no history of cardiovascular disease or cancer. Investigators did not detect an increase in omega-3 and AFib risk in this group treated with 1 gram of EPA and DHA daily.

Read Dr. Radford’s 5 key takeaways about the VITAL Study Omega-3 and cardiovascular disease prevention.

Refer to the summary table below of four recent trials—REDUCE-IT, OMEMI, STRENGTH and VITAL Rhythm Study—and their outcome data regarding AFib. While the development of AFib was not a primary outcome measurement in any of these trials, it was reported as an adverse event.

Omega-3 Fatty Acid Supplementation and Risk of Atrial Fibrillation (AFib)

Trial Omega-3 Study Population Primary Endpoint Atrial Fibrillation (AFib)
REDUCE-IT1
Primary Composite Endpoint: Cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina
Purified EPA 4 grams daily vs. mineral oil placebo N = 8,179 (71% for secondary prevention)

  • Men and women ≥45
  • with established atherosclerotic cardiovascular disease (ASCVD)
  • or with diabetes and other risk factors
  • On statin therapy (LDL 41-100 mg/dL)
  • triglycerides 135 to 499 mg/dL
Primary end-point event reduced in treatment group vs placebo (17.2% vs 22.0% HR, 0.75; 95% CI 0.68 to 0.83; P<0.001) Significant increase in any AFib in treatment group vs. placebo (5.3% vs. 3.9%, p=0.03) Significant Increase in hospitalization  for AFib in treatment group vs. placebo (3.1% vs. 2.1%, P=0.004).
OMEMI2
Primary Composite Endpoint: Nonfatal myocardial infarction, stroke, emergent revascularization, all-cause death, or heart failure hospitalization
EPA + DHA 1.8 grams daily vs. corn oil placebo N = 1,027

  • Older adults (age 70-82) after acute myocardial infarction (in last 2-8 weeks)
  • All participants from Norway, with higher baseline EPA concentrations, compared to those in North America
No significant difference in primary endpoint between treatment group vs placebo (21.4% vs. 20.0%; HR 1.08, 95% CI 0.82-1.41, p=0.06) Numerically higher rate of new-onset AFib in the treatment group vs. placebo. Not statistically significant (smaller study).  (7.2% vs. 4.0%; HR 1.84, 95% CI 0.98-3.45).
STRENGTH3
Primary Composite Endpoint: Cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization
EPA + DHA 4 grams daily vs. corn oil placebo N= 13,078

  • Established atherosclerotic cardiovascular disease (ASCVD) involving the coronary, peripheral, carotid, or aortic territories)
  • age ≥40 years with diabetes mellitus (type 1 or 2) plus ≥ 1 additional risk factor (chronic smoking, hypertension, hs-CRP ≥ 2 mg/L, or moderate albuminuria)
  • men ≥50, women ≥60  with ≥ 1 additional risk factor, including a family history of premature coronary artery disease (CAD), chronic smoking, hs-CRP ≥ 2 mg/L, impaired kidney function, or coronary artery calcium (CAC)  > 300;
  • elevated triglycerides (180-500 mg/dL);
  • low HDL (men < 42, women < 47);
  • on optimal statin therapy (LDL<100)
No significant difference in primary endpoint between treatment group vs. placebo (12.0% vs. 12.2%; HR 0.99, 95% CI 0.90-1.09, p=0.84). Significant increase in new-onset AFib in treatment group vs. placebo. (2.2% vs. 1.3%; HR 1.69, 95% CI 126-2.21).
VITAL Rhythm Study4
Primary Composite Endpoint: Incident AFib confirmed by Medical Record Review
EPA + DHA 840 mg vs. placebo N = 25,119

  • Men ≥ 50 and women ≥55;
  • No history of  cardiovascular disease (myocardial infarction, stroke, transient ischemic attack, angina, or revascularization) or cancer
No effect on EPA-DHA on incident AFib (3.7% vs 3.4%, HR, 1.09; 95% CI, 0.96-1.24; P = 0.19)

Q: How do the results of these studies change how you treat your patients?

A: Because an increased risk of AFib has been associated with an intake of 4 grams per day of omega-3 fatty acid supplement, I recommend that my high-risk patients take less than that amount.

How much less? There is one small trial, OMEMI, in which older Norwegian participants with a recent prior heart attack were treated with 1.8 grams of omega-3 per day or placebo. This trial did not demonstrate an increased risk of AFib. Based on the limited data of this clinical trial, I recommend 2 grams of omega-3 per day to my higher risk patients to avoid an increased risk of developing atrial fibrillation. That being said, some of these patients may take higher doses of omega-3 supplements to treat other conditions, such as high triglycerides. Sometimes we just need to weigh the risks and benefits of treatments on a case-by-case basis.

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Q: Should high-risk patients also limit the omega-3 intake in their diet?

A: These studies do not address the association of dietary intake of omega-3 with risk of developing AFib. I don’t routinely recommend patients limit their dietary intake of omega-3 because most individuals do not consume the recommended two servings of fatty fish per week, which are rich in omega-3. I am still more likely to recommend patients add these fatty fish food sources of omega-3 to their diet rather than avoid it. The value of omega-3 from dietary sources was demonstrated in the primary results from the VITAL study (also the source of data used in the VITAL Rhythm Study previously discussed). In participants who were eating two or more servings of fish per week, there was no benefit of adding 1 gram of omega-3 daily to reduce cardiovascular risk. However, in those participants who were not eating one or two servings of fish per week, the addition of 1 gram of omega-3 reduced their risk of heart attack, stroke or death from cardiovascular causes by almost 20%.

As a reminder, your health care provider understands your health profile best, including your medical history, risks and current medication and supplement use. It is important to talk to him or her about which supplements, including omega-3, are best for you.

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Omega-3 and AFib Risk Article provided by Nina B. Radford, MD, Cooper Clinic Cardiologist and Director of Clinical Research.

References

1Bhatt DL, Steg PG, Miller M, et al.; REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380(1):11-22. doi:10.1056/NEJMoa1812792

2Kalstad AA, Myhre PL, Laake K, et al; OMEMI Investigators. Effects of n-3 fatty acid supplementation in elderly patients after myocardial infarction: a randomized, controlled trial. Circulation. 2021;143(6):528-539. doi:10.1161/CIRCULATIONAHA.120.052209

3Nicholls SJ, Lincoff AM, Garcia M, et al. Effect of high-dose omega-3 fatty acids vs. corn oil on major adverse cardiovascular events in patients at high cardiovascular risk: the STRENGTH randomized clinical trial. JAMA. 2020;324(22):2268-2280. doi:10.1001/jama.2020.22258

4Albert CM, Cook NR, Pester J, et al. Effect of marine omega-3 fatty acid and vitamin D supplementation on incident atrial fibrillation: a randomized clinical trial. JAMA. Published March 16, 2021. doi:10.1001/jama.2021.1489

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