The EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study programme: Design and exposure accrual for an evaluation of empagliflozin in routine clinical care

BACKGROUND: The EMPA‐REG OUTCOME trial showed that empagliflozin reduced the risk of cardiovascular death and hospitalization for heart failure (HHF) in diabetic patients with cardiovascular disease. EMPRISE is a study programme on the effectiveness, safety and healthcare utilization of empagliflozin in routine care, leveraging real‐world data from two commercial and one federal US data sources from 2014 to 2019. OBJECTIVES: To describe rationale and design of EMPRISE, assess ability to minimize confounding and evaluate the time to reach sufficient statistical power for a key study outcome, HHF, using baseline information from the first year of EMPRISE. METHODS: In 3 claims data sets, we identified a 1:1 propensity score (PS)‐matched cohort of diabetic patients ≥18 years initiating empagliflozin or a dipeptidyl peptidase‐4 inhibitor (DPP4i), resulting in 6643 total pairs. The PS model included >140 baseline covariates. We measured covariate balance via standardized differences (SD) and postmatching c‐statistic. We computed the incidence rate (IR) of HHF, predicted exposure accrual over time and calculated expected power. RESULTS: After PS matching, patient characteristics were balanced with SD <0.1 and c‐statistic between 0.54 and 0.59. The population IR of HHF was 4.4 per 1000 person‐years using a specific HHF definition and 14.8 using a broader HHF definition. In our projection, 80%‐powered analyses would require a minimum of 169 HHF events, expected to accumulate by year 3 (specific definition) or year 2 (broader definition). CONCLUSION: Baseline information from EMPRISE provided evidence of solid confounding control and adequate exposure accrual with expected powered analyses for the primary outcomes.