Abstract 14959: Effect of Empagliflozin on Total Events of Myocardial Infarctions by Subtype in the EMPA-REG OUTCOME Trial

Abstract

Introduction: In EMPA-REG OUTCOME®, the sodium-glucose transporter inhibitor, empagliflozin (EMPA), reduced the risk of first cardiovascular (CV) events primarily CV mortality and hospitalization for heart failure in patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease. In analyses including total events, EMPA also reduced the risk of myocardial infarction (MI). Here we report the effects of EMPA on the total number of MIs by subtype. Methods: Patients were randomized to receive EMPA 10 mg, EMPA 25 mg, or placebo. We assessed the effect of pooled EMPA versus placebo on total (first plus recurrent) events of fatal and non-fatal MI using a negative binomial model with robust confidence intervals (CI) that preserves randomization and accounts for the within-patient correlation of multiple events. Post-hoc, we analyzed established subtypes of MI: Type 1: Typically related to plaque-rupture or thrombus; Type 2: Supply-demand; Type 3: Sudden-death related (i.e., fatal MI); Type 4: Percutaneous coronary intervention related; and Type 5: Coronary artery bypass graft related. Except type 3 MIs, MIs were non-fatal. The MIs, including subtypes, were centrally adjudicated and could be assigned to more than one subtype. Results: 7,020 patients were treated. Overall, there was 421 total events of MIs. Specifically, 299, 86, 26, 19, and 1 of the MIs were classified as type 1, 2, 3, 4, and 5 MIs, respectively (not mutually exclusive). Overall, EMPA reduced the risk of total events of MI by 21% versus placebo (rate ratio [95% CI], EMPA versus placebo: 0.79 [0.620; 0.998], p=0.0486; each MI only counted once). The overall reduction in total events of MIs by EMPA was driven by the effect on type 1 and 2 MIs, as well as type 3 MIs, with limited number of type 4 and 5 MIs (Figure). Conclusions: EMPA reduced the risk of total MI events with consistent effects across the most common etiologies, the type 1 (plaque-rupture or thrombus) and 2 (supply-demand) MIs.