STRENGTH Analysis Questions Cardioprotective Benefits of Fish Oil-Based Therapies

Patrick Campbell

A secondary analysis of the STRENGTH trial from ACC.21 is calling into question the apparent CV benefits of other fish oil-based agents in patients with elevated triglycerides.

An analysis of the STRENGTH trial is shedding further light on the relationship between use of fish oil-based therapies and risk of cardiovascular disease, according to study presenters.

A secondary analysis examining the impact of AstraZeneca’s omega-3 carboxylic acid therapy Epanova, investigators used data from the study to assess the impact of achieved plasma levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) did not influence risk of cardiovascular outcomes among the more than 6500 patients receiving the EPA-DHA compound during the trial.

“This is an intensely controversial area. One fish oil trial after another has been neutral, but REDUCE-IT reported a striking 25% reduction in events compared with a placebo pill containing mineral oil. But in our analysis, among patients treated with fish oil we found no evidence that EPA is beneficial or that DHA is harmful,” said lead investigator Steven Nissen, MD, Chief Academic Officer of the Heart, Vascular, and Thoracic Institute at the Cleveland Clinic, in a statement. “So, we have many patients taking fish oils but no evidence that they have favorable effects on the heart.”

In recent years, few trials in cardiovascular medicine have garnered the attention REDUCE-IT has commanded since released at AHA 2018. While STRENGTH examined a different agent and failed to demonstrate significant benefit, some have used data from the trial as an avenue to further assess icosapent ethyl and results of REDUCE-IT.

In the current analysis, which was presented at the American College of Cardiology’s 70th Annual Scientific Sessions (ACC.21), investigators examined a subset of 10,382 patients from the 13,078-patient trial with information related to omega-3 fatty acid levels. With data from 5175 patients receiving treatment and 5207 patients receiving placebo, investigators grouped patients into tertiles based on plasma EPA and DHA levels.

Click here to hear the reaction to STRENGTH data from Deepak Bhatt, MD, MPH.

Of note, the median plasma EPA level for patients on treatment was 89 (46-131) µg/mL and the top tertile level was 151 (132-181) µg/mL. For DHA< the median plasma level was 91 (71-114) µg/mL and the top tertile level was 118 (102-143) µg/mL.

Upon analysis, investigators observed adjusted hazard ratios for the highest tertile of EPA and DHA were 0.98 (95% CI, 0.83-1.16; P=.81) and 1.02 (95% CI, 0.86-1.20; P=.85), respectively. Further analysis indicated there were no differences in the occurrence of the primary outcome when assessing patients based on those within the lowest tertiles or changes in EPA or DHA over time in the study.

“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 added. “All of these analyses showed no benefits or harms.”

Additionally, investigators pointed out an apparent increase in risk for atrial fibrillation among patients receiving omega-3 carboxylic acid. Specifically, results indicated patients randomized to the treatment arm of STRENGTH had a 69% increased risk of new-onset atrial fibrillation (HR, 1.69; 95% CI, 1.29-2.21).

For more insight into this analysis of the STRENGTH trial, Practical Cardiology reached out to Nissen and that conversation is the subject of this ACC.21 House Call.

This study, “Association Between Achieved ω-3 Fatty Acid Levels and Major Adverse Cardiovascular Outcomes in Patients With High Cardiovascular Risk,” was presented at ACC.21 and simultaneously published in JAMA.