P824The clinical impact of polyunsaturated fatty acid on clinical outcomes in acute coronary syndrome with dyslipidemia: HIJ-PROPER sub-analysis

Abstract

Abstract Background Polyunsaturated fatty acids, especially omega-3 and -6 series, are key essential nutrients that play an important role in humans to maintain cell membranes and function. A recent randomized trial reported that adding eicosapentaenoic acid (EPA) to statins was beneficial to cardiovascular disease patients who had a residual risk factor. Further, several studies have reported that the low baseline value for EPA to arachidonic acid (AA) ratio is related to worse clinical outcome and plaque vulnerability in coronary artery disease patients. However, effects of baseline EPA/AA ratio on clinical outcomes in ACS patients have not been thoroughly evaluated. Objectives This study aimed to examine the impact of baseline eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio on clinical outcomes of acute coronary syndrome (ACS) patients and how lipid-lowering therapy affects serum EPA/AA levels in these patients. Methods This is a sub-analysis of HIJ-PROPER assessing the effect of aggressive low-density lipoprotein cholesterol (LDL-C)-lowering treatment with pitavastatin+ezetimibe in 1,734 ACS patients with dyslipidemia. Patients were divided into two groups based on EPA/AA level on admission (cut-off: 0.34 μg/mL; median of baseline EPA/AA level) and clinical outcomes were examined. Results Percent reduction of LDL-C from baseline to follow-up and mean LDL-C level during follow-up were similar regardless of baseline EPA/AA ratio. In the low EPA/AA group, the Kaplan–Meier estimate for the primary endpoint at 3 years was 27.2% in the pitavastatin+ezetimibe group, compared with 36.6% in the pitavastatin-monotherapy group [hazard ratio (HR), 0.69; 95% confidence interval (CI), 0.52–0.93; P=0.015). However, in the high EPA/AA group, there was no significant reduction in the primary endpoint by pitavastatin+ezetimibe therapy (HR, 0.92; 95% CI, 0.70–1.20; P=0.52). Conclusions Aggressive lipid-lowering therapy with ezetimibe had a positive effect on clinical outcomes in the low EPA/AA group of ACS patients with dyslipidemia, but not in the high EPA/AA group. This effect was independent of LDL-C reduction and suggests that EPA/AA measurement on admission in ACS patients contributes to a “personalized” lipid-lowering approach.