Effectiveness of Icosapent Ethyl on First and Total Cardiovascular Events in Patients with Metabolic Syndrome, but without Diabetes: REDUCE-IT MetSyn

Abstract Introduction Metabolic Syndrome (MetSyn) is associated with high risk of cardiovascular (CV) events, irrespective of statin therapy. In the overall REDUCE-IT study of statin-treated patients, icosapent ethyl (IPE) reduced the risk of the primary composite endpoint (CV death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization) and the key secondary composite endpoint (CV death, nonfatal myocardial infarction, or nonfatal stroke). Methods REDUCE-IT was an international, double-blind trial that randomized 8179 high CV risk statin-treated patients with controlled low density lipoprotein cholesterol (LDL-C), and elevated triglycerides, to IPE 4 grams/day or placebo. The current study evaluated the prespecified patient subgroup with a history of MetSyn, but without diabetes at baseline. Results Among patients with MetSyn but without diabetes at baseline (n=2866), the majority (99.8%) of this subgroup were secondary prevention patients. IPE use was associated with a 29% relative risk reduction for the first occurrence of the primary composite endpoint (hazard ratio [HR], 0.71 [95% CI, 0.59-0.84]; P <0.0001, absolute risk reduction [ARR]=5.9%; number needed to treat [NNT]=17) and 41% reduction in total (first plus subsequent) events (rate ratio [RR], 0.59 [95% CI, 0.48-0.72]; P <0.0001) compared with placebo. The risk for the key secondary composite endpoint was reduced by 20% (P=0.05) and a 27% reduction in fatal/nonfatal MI (P=0.03), 47% reduction in urgent/emergent revascularization (P <0.0001) and 58% reduction in hospitalization for unstable angina (P <0.0001). Non-statistically significant reductions were observed in cardiac arrest (44%) and sudden cardiac death (34%). Conclusion(s) In statin-treated patients with a history of MetSyn, IPE significantly reduced the risk of first and total CV events in REDUCE-IT. The large relative and absolute risk reductions observed supports IPE as a potential therapeutic consideration for patients with MetSyn at high CV risk.