Omega-3 supplements may up risk of AF

Taking omega-3 supplements is associated with an increased risk developing atrial fibrillation (AF) among people with high triglyceride levels, according to a meta-analysis of five randomized controlled trials (RCTs).

“Currently, fish oil supplements are indicated for patients with elevated plasma triglycerides to reduce cardiovascular [CV] risk,” said study principal investigator Dr Salvatore Carbone from Virginia Commonwealth University in Richmond, Virginia, US. “The CV benefits, however, have been inconsistent.”

“Due to the high prevalence of elevated triglycerides in the population, they can be commonly prescribed,” he continued. “Of note, low dose omega-3 fatty acids [FA] are [also] available over the counter, without the need for a prescription.”

The meta-analysis included five RCTs (REDUCE-IT, ASCEND, R&P, STRENGTH, OMEMI) involving a total of 50,277 patients with elevated triglyceride levels who had established CV disease or at high risk for CV disease. They were randomized to receive supplements containing omega-3 fatty acids (with doses varying between 0.84 to 4 g per day, depending on trials) or matching placebo, and were followed up for a period between 2 to 7.4 years. [Eur Heart J Cardiovasc Pharmacother 2021;doi:10.1093/ehjcvp/pvab008]

Participants taking omega-3 supplements had significantly higher risk of AF, by an excess of 37 percent, compared with the placebo group (incidence rate ratio [IRR], 1.37, 95 percent confidence interval [CI], 1.22–1.54; p<0.001).

The studies included did not show significant heterogeneity nor publication bias, according to the authors.

For sensitivity analysis, they also included the VITAL rhythm trial, which was presented at AHA 2020 Congress but the complete data has yet to be fully disclosed. Similarly, the risk of AF remained greater in the omega-3 supplement group compared with the placebo group (IRR, 1.29, 95 percent CI, 1.13–1.48; p=0.0002).

“Our study suggests that fish oil supplements are associated with a significantly greater risk of AF in patients at elevated CV risk. Although one clinical trial indicated beneficial CV effects of supplementation, the risk for AF should be considered when such agents are prescribed or purchased over the counter, especially in individuals susceptible to developing the heart rhythm disorder,” said Carbone.

While trials investigating the CV benefits of omega-3 supplements have yielded inconsistent results, the association between omega-3 FA supplementation and an increased risk of AF persisted in most trials.

“Even lower doses of omega-3 FA supplementation has shown a potential signal for increased risk for AF, proposing that regardless of the dose of omega-3 FA supplementation implemented in the trials and potential-related benefits on CV outcomes, omega-3 FA supplementation may increase the risk for AF,” said Carbone and co-authors.

“The results of our meta-analysis confirmed this finding, which is concerning given the large proportion of patients eligible for treatment with omega-3 FA supplementation.”

However, the mechanisms underlying the increased AF risk with omega-3 FA supplementation remain unclear thus far, and hence, more mechanistic clinical trials are required to elucidate this, suggested the researchers.