Generalizability of REDUCE-IT eligibility criteria in a large diabetes cardiovascular outcomes trial: A post hoc subgroup analysis of EMPA-REG outcome: Analysis of EMPA-REG OUTCOME using REDUCE-IT criteria.

Objectives: REDUCE-IT showed that icosapent ethyl (IPE) improved cardiovascular (CV) outcomes in participants with established CV disease (CVD) or type 2 diabetes (T2D) and at least one additional risk factor plus mild-moderate hypertriglyceridemia and reasonably controlled low-density lipoprotein cholesterol (LDL-C). As the generalizability of REDUCE-IT has not been investigated in a T2D population with established CVD, this Methods: Participants from EMPA-REG OUTCOME were screened for inclusion using both REDUCE-IT-like criteria (baseline statin therapy, triglycerides 135-499 mg/dL and LDL-C 41-100 mg/dL) and slightly amended FDA indication criteria (triglycerides ≥150 mg/dL). Analyses were conducted to characterize the study population and CV outcomes in participants eligible for IPE versus those not eligible for IPE. Results: Of the 7020 participants from EMPA-REG OUTCOME, 1810 (25.8%) fulfilled REDUCE-IT criteria and 3182 (45.3%) fulfilled FDA criteria for IPE treatment. Treatment effects of empagliflozin versus placebo on CV and kidney outcomes and mortality were consistent in participants meeting REDUCE-IT and FDA criteria and those who did not. Conclusions: These results indicate that a sizable proportion of patients with diabetes and established CVD, such as those in EMPA-REG OUTCOME, may be eligible for IPE treatment to lower residual CV risk. Treatment benefit with empagliflozin was consistent, regardless of REDUCE-IT or FDA eligibility criteria.