Effects of Eicosapentaenoic Acid vs Eicosapentaenoic/Docosahexaenoic Acids on Cardiovascular Mortality

Abstract

Background

Purified eicosapentaenoic acid (EPA) and mixed eicosapentaenoic/docosahexaenoic acids (EPA/DHA) are omega-3 polyunsaturated fatty acids (n-3 PUFAs) of interest for preventing cardiovascular disease (CVD) as adjunct to statins. Randomized clinical trial (RCT) evidence continues to emerge, including data from the RESPECT-EPA (Randomized Trial for Evaluation in Secondary Prevention Efficacy of Combination Therapy–Statin and Eicosapentaenoic Acid) trial, but n-3 PUFAs’ roles in prevention remains controversial.

Objectives

The objective of the study was to assess the efficacy of EPA vs EPA/DHA compared to the standard preventive therapy across published RCTs investigating the use of n-3 PUFAs for primary or secondary prevention of CVD.

Methods

Following a prespecified protocol registered in the PROSPERO database (CRD42023390587), we identified RCTs reporting CVD-attributable mortality in patients randomized to EPA, EPA/DHA, or a standard preventive therapy for primary or secondary CVD prevention. We used random effects meta-analysis to estimate pooled HRs of CVD-attributable mortality achieved with EPA or EPA/DHA relative to the standard preventive therapy.

Results

Sixteen RCTs met the inclusion criteria, representing 127,771 patients in total (41% women, mean age 64 ± 5 years). Median follow-up was 3.7 years (IQR: 2.7-5.0 years). Compared to the standard preventive therapy, CVD-attributable mortality was significantly reduced with purified EPA (HR: 0.79 [95% CI: 0.67-0.94]; P = 0.006); this effect was less for EPA/DHA (HR: 0.92 [95% CI: 0.84-1.00]; P = 0.044).

Conclusions

EPA lowered incident CVD-attributable mortality in RCTs investigating its use for primary or secondary CVD prevention. Relative to EPA, benefits reported with EPA/DHA were attenuated. Although more work is needed to understand these differences, EPA should preferentially be used in cardiovascular conditions for which it is indicated.