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

Subodh Verma; Andrew Kosmopoulos; Deepak L Bhatt; David Fitchett; Anne Pernille Ofstad; Christoph Wanner; Michaela Mattheus; Bernard Zinman; Patrick R Lawler; Lawrence A Leiter

doi:10.1016/j.ajpc.2023.100510

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

Am J Prev Cardiol. 2023 Jun 10:15:100510. doi: 10.1016/j.ajpc.2023.100510. eCollection 2023 Sep.

Authors

Affiliations

¹ Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
² Mount Sinai Heart, Icahn School of Medicine at Mount Sinai Health System, New York City, NY, United States.
³ St Michael's Hospital, Division of Cardiology, University of Toronto, Toronto, ON, Canada.
⁴ Boehringer Ingelheim Norway Ks, Asker, Norway.
⁵ Oslo Diabetes Research Center, Oslo, Norway.
⁶ Würzburg University Clinic, Würzburg, Germany.
⁷ Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
⁸ Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
⁹ Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada.
¹⁰ Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, ON, Canada.

Abstract

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 post hoc analysis investigated how many participants from EMPA-REG OUTCOME, which tested the effects of empagliflozin versus placebo on CV outcomes in participants with T2D and CVD, would have been eligible for IPE treatment, and whether CV outcomes differed based on eligibility for IPE treatment.

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.

Keywords: Cardiovascular disease; Icosapent ethyl; Omega-3 fatty acids; Triglycerides; Type 2 diabetes.