Patients at high risk for cardiovascular events who had the highest blood eicosapentaenoic acid (EPA) levels one year after taking prescription fish oil daily showed no significant difference from those taking a corn oil placebo, the American College of Science Session Cardiology suggests.
“This is an extremely controversial area,” said lead study author Steven Nissen, MD, MACC, a cardiologist at Cleveland Clinic, of the study. “One fish oil trial after another was neutral, but REDUCE-IT saw a remarkable 25% reduction in events compared to a placebo pill that contained mineral oil. However, in our analysis, we found no evidence that EPA is beneficial or DHA harmful in patients treated with fish oil. So we have a lot of patients taking fish oils, but no evidence that they are beneficial for the heart. “
The post hoc analysis of the STRENGTH study, which enrolled more than 13,000 people at high risk for serious adverse cardiovascular events, randomized to 4 g omega-3 carboxylic acid (combined EPA and docosahexaenoic acid) per day [DHA]) or a corn oil placebo. The primary composite endpoint was cardiovascular death, myocardial infarction, stroke, need for revascularization, or chest pain requiring hospitalization. The authors of STRENGTH reported no differences between the study groups with regard to the primary study result.
The current analysis examined more than 10,300 patients with available omega-3 fatty acids. Events were reported in 11.1% of patients treated with fish oil and 11% in the placebo group with corn oil. The event rate for the top tertile of the DHA achieved was 11.4%.
“To be thorough, we examined the data in a number of ways – absolute EPA and DHA levels, changes in levels of these omega-3s, levels of red blood cells, and by subgroups of primary and secondary prevention,” added Dr. Nits added. “None of these analyzes showed any advantages or disadvantages.”
Dr. Nissen also cited several possible reasons for the discrepancies between the STRENGTH and REDUCE-IT results.
“It could be that EPA is really beneficial, or it could be that adding DHA to STRENGTH has done harm and thereby undermined the benefits of EPA. However, the current study found no benefit from EPA and no harm from DHA, ”he said. “Alternatively, the different results of these studies could have occurred because REDUCE-IT used mineral oil as a placebo, which led to a false positive study. Unlike inert corn oil, mineral oil has significant adverse effects. If you give a toxic placebo, the active ingredient may look very good. “
The study was simultaneously published in JAMA Cardiology.
Nissen S. Relationship Between Omega-3 Fatty Acid Levels and Major
Adverse cardiovascular outcomes in patients at high cardiovascular risk. Presented at: American College of Cardiology Scientific Session. 15.-17. May 2021.