QUALIFYING EVENT PROXIMITY, CARDIOVASCULAR RISK, AND BENEFIT OF EMPAGLIFLOZIN IN PATIENTS WITH TYPE 2 DIABETES AND STABLE ATHEROSCLEROSIS IN THE EMPA-REG OUTCOME TRIAL

Abstract

In type 2 diabetes, the temporal proximity of an atherosclerotic cardiovascular (CV) event can impact prognosis, but whether timing influences sodium glucose co-transporter 2 inhibitor effects is unknown. We explored the association of time from last qualifying CV event before randomization (myocardial infarction [MI], stroke, coronary artery disease or peripheral arterial disease) with CV outcomes and benefit of empagliflozin in the EMPA-REG OUTCOME trial. Patients were randomized to empagliflozin 10 mg, 25 mg or placebo with a median follow-up of 3.1 years. Risk of major adverse CV events (3-point major adverse CV events: CV death, MI, stroke), CV death or hospitalization for heart failure (HHF) were evaluated using Cox regression in subgroups of ≤1 versus >1 year since last qualifying CV event. Qualifying event stratification was possible in 6796 (97%) patients. In the overall population (N=6796; 4547 empagliflozin and 2249 placebo patients), the median (Q1, Q3) time from last CV event was 3.8 (1.5–7.6) years. Overall, 1214 (empagliflozin 841; placebo 373) and 5582 (empagliflozin 3706; placebo 1876) patients had a last qualifying CV event ≤1 and >1 year, respectively. Patients with more recent events had similar risk for CV outcomes compared with patients >1 year from the qualifying event (Figure). Moreover, the benefit of empagliflozin on CV outcomes was consistent between patients enrolled ≤1 or >1 year from the qualifying CV event (all p-interaction >0.05; Figure). Although most patients had a qualifying CV event >1 year before randomization in the EMPA-REG OUTCOME trial, the benefits of empagliflozin appear to extend to patients with more recent CV events.