Abstract

The EMPA-REG OUTCOME trial showed cardioprotective effects of empagliflozin (EMPA) in patients with established cardiovascular diseases (CVD). Within the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) multi-database study of patients in routine care, we evaluated the relative cardiovascular benefits of EMPA versus therapeutic alternatives in older patients with type 2 diabetes (T2D) across the broad spectrum of cardiovascular risk. Using Medicare data (08/2014-09/2018), we identified 31,719 pairs of 1:1 propensity score-matched (PSM) T2D patients ≥65 years initiating EMPA or a GLP-1RA [Cohort 1], and 23,307 pairs initiating EMPA or a DPP-4i [Cohort 2]. We assessed (i) a modified major adverse cardiovascular event (MACE) outcome (MI, stroke, all-cause mortality) and (ii) hospitalization for heart failure (HHF) in primary discharge position. In each cohort, we estimated hazard ratios (HR) and rate differences (RD) per 1,000 person years of follow-up, adjusting for >140 baseline covariates and accounting for death as a competing risk, overall and in subgroups (i) with and (ii) without baseline CVD (that includes atherosclerotic CVD and HF). After PSM, exposure groups had similar characteristics (Table 1). Compared to GLP-1RA, EMPA had a similar risk of the modified MACE outcome [HR (95% CI): 1.05 (0.93,1.18)] and a reduced risk of HHF [HR 0.70 (0.57,0.86)]. Absolute benefit for HHF was larger in patients with CVD [RD -6.24 (-9.92, -2.56)] than in patients without CVD [RD -0.81 (-2.15, 0.54)]. Compared to DPP-4i, EMPA reduced the risk of both modified MACE outcome [HR: 0.67(0.59,0.77)] and HHF [HR: 0.46 (0.37,0.57)]. For both outcomes, the absolute benefit with EMPA was larger among patients with CVD compared to those without CVD. EMPA reduced the risk of HHF vs. GLP-1RA and DPP-4i and the risk of a modified MACE outcome vs. DPP-4i. The absolute benefit associated with EMPA was larger among patients with CVD compared to those without CVD.

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