A post-hoc analysis sought to elucidate the contradictory results between the STRENGTH and REDUCE-IT trials.
A new post-hoc analysis of the STRENGTH trial suggests that omega-3 fatty acids from prescription fish oil may have no effect on cardiovascular event reduction.
These findings were presented at the American College of Cardiology (ACC) Annual Scientific Session.
Investigators from the double-blind, multienter STRENGTH trial reported neutral results between patients who consumed a mixture of EPA and docosahexaenoic acid (DHA) and patients who received a placebo.
On the other hand, results from the REDUCE-IT trial showed that patients who consumed omega-3 CA experienced a 25% reduction in events compared with a patients who took a mineral oil placebo pill.
Thus, a team of investigators, led by Steven Nissen, MD, MACC, Cleveland Clinic, sought to reconcile the conflicting evidence between the studies.
First, they evaluated a subset of the 13,078 individuals from the STRENGTH trial (n = 10,382). Of this subgroup, 5175 had received omega-3 carboxylic acid and 5,207 received corn oil.
The average age of the population was 62.5 years, a majority (2/3) were men, and a third of patients had diabetes.
As such, they found that cardiosvascular events—such as cardiovascular death, heart attack, stroke, need for procedures to open blocked arteries or chest pain that required hospitalization—occurred in 11.1% and 11% of omega-3 and placebo patients, respectively.
Nissen and team then used available bloodwork to divide the population into tertiles according to EPA and DHA levels achieved. Patients were assessed at baseline and 12 months post-randomization.
Overall, the top tertile achieved EPA levels of 151 (132-181) μg/mL and DHA levels 118 (102-143) μg/mL—compared with median EPA and DHA levels of 89 (46-131) μg/mL and 91 (71-114) μg/mL.
Similar to the overall findings, there were no differences in cardiovascular event rate between top EPA and DHA tertiles and placebo cohorts.
“To be thorough, we looked at the data multiple ways—absolute EPA and DHA levels, change in levels of these omega-3 fatty acids, red blood cell levels, and by primary and secondary prevention subgroups,” Nissen said in a press release. “All of these analyses showed no benefits or harms.”
He explained several potential underlying factors, including the possibility that DHA may counteract any possible benefit offered by EPA—although he noted that their post-hoc analysis showed no benefit from EPA or harm for DHA.
A possible explanation for REDUCE-IT’s results could be the use of mineral oil, which could have caused major adverse effects and, therefore, resulted in a false positive trial.
Nissen’s team also examined potential harmful effects from fish oil. Although not considerable, patient increase in new onset atrial fibrillation among fish oil patients was 69%. The condition thus occurred in 2.2% of patients in the fish oil group—versus 1.3% in the corn oil group.
“Fish oils increase the risk of atrial fibrillation substantially, and there is no solid evidence that they help the heart in anyway,” Nissen remarked. “It’s a sad story for cardiology.”
The team indicated that research to compare mineral oil with corn oil, as well as purified EPA and other formulations of omega-3 fatty acids are warranted.
The study, “Relationship Between Omega-3 Fatty Acid Levels and Major Adverse Cardiovascular Outcomes In Patients With High Cardiovascular Risk,” was presented at ACC 2021.