Abstract/Description
Introduction: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated cardioprotective and renoprotective benefits in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). However, the effects of these agents in patients with end-stage renal disease (ESRD) or on dialysis remain underexplored, as previous clinical trials often excluded this population. With the recent removal of ESRD as a contraindication by the U.S. Food and Drug Administration, understanding the cardiovascular risks of SGLT2 inhibitors in this group is imperative. This study aimed to assess the incidence of new onset heart failure (HF), including HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF), among patients with ESRD or on dialysis treated with SGLT2 inhibitors compared to matched controls.
Materials and Methods: We conducted a retrospective cohort study using the TriNetX U.S. Collaborative Network, which includes de-identified electronic medical records from 50 healthcare organizations. Patients aged 18–85 with a diagnosis of ESRD or CKD stage 5, glomerular filtration rate < 15 ml/min, or undergoing dialysis were included. Those with prior diagnoses of HF or type 1 diabetes mellitus were excluded. SGLT2 inhibitor use was identified using Anatomical Therapeutic Chemical (ATC) classification code A10BK. Propensity score matching was used to balance cohorts based on demographics, comorbidities, and medication usage. The primary outcome was new onset HF (ICD-10 codes I50, I11.0), with secondary outcomes including HFrEF (I50.2) and HFpEF (I50.3). Additional comparative analyses were run with exclusion criteria of prior history of type 2 diabetes mellitus (T2DM) or dialysis. Statistical analyses included relative risk calculations and Kaplan-Meier survival analysis, with significance defined as P < 0.05.
Results: After propensity score matching, 47,894 patients were included in both the SGLT2 inhibitor and control cohorts. The incidence of new-onset HF was higher in the SGLT2 inhibitor group compared with controls (2.96% vs. 1.32%), with increased risk for both HFrEF (2.27% vs. 0.57%) and HFpEF (1.86% vs. 0.88%). Relative risks for new-onset HF, HFrEF, and HFpEF were 2.25 (95% CI), 3.96 (95% CI), and 2.11 (95% CI), respectively. In a subgroup excluding patients with prior T2DM (n=8,657), relative risks further increased to 8.73, 14.39, and 5.55, respectively.
Discussion: Our findings suggest that SGLT2 inhibitors may not confer the same cardioprotective effects in patients with ESRD or those undergoing dialysis as seen in earlier-stage CKD populations. This reduced efficacy may be attributed to diminished glomerular filtration rate and tubular function, both of which are essential for the diuretic and natriuretic mechanisms that contribute to SGLT2 inhibitors’ benefits. Prior studies, including DAPA-CKD and EMPA-KIDNEY, demonstrated mixed results on HF outcomes in patients with advanced kidney disease. These results raise caution regarding the generalized use of SGLT2 inhibitors in patients with advanced kidney dysfunction.
Conclusion: This study demonstrates a higher incidence of new onset heart failure, HFrEF, and HFpEF in patients with ESRD or on dialysis who are treated with SGLT2 inhibitors compared to matched controls.
Faculty Advisor/Mentor
Amin Yehya
Faculty Advisor/Mentor Department
Cardiology
College/School/Affiliation
Sentara
Included in
New Onset Heart Failure of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors in Patients with End-Stage Renal Disease (ESRD) and Dialysis
Introduction: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated cardioprotective and renoprotective benefits in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). However, the effects of these agents in patients with end-stage renal disease (ESRD) or on dialysis remain underexplored, as previous clinical trials often excluded this population. With the recent removal of ESRD as a contraindication by the U.S. Food and Drug Administration, understanding the cardiovascular risks of SGLT2 inhibitors in this group is imperative. This study aimed to assess the incidence of new onset heart failure (HF), including HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF), among patients with ESRD or on dialysis treated with SGLT2 inhibitors compared to matched controls.
Materials and Methods: We conducted a retrospective cohort study using the TriNetX U.S. Collaborative Network, which includes de-identified electronic medical records from 50 healthcare organizations. Patients aged 18–85 with a diagnosis of ESRD or CKD stage 5, glomerular filtration rate < 15 ml/min, or undergoing dialysis were included. Those with prior diagnoses of HF or type 1 diabetes mellitus were excluded. SGLT2 inhibitor use was identified using Anatomical Therapeutic Chemical (ATC) classification code A10BK. Propensity score matching was used to balance cohorts based on demographics, comorbidities, and medication usage. The primary outcome was new onset HF (ICD-10 codes I50, I11.0), with secondary outcomes including HFrEF (I50.2) and HFpEF (I50.3). Additional comparative analyses were run with exclusion criteria of prior history of type 2 diabetes mellitus (T2DM) or dialysis. Statistical analyses included relative risk calculations and Kaplan-Meier survival analysis, with significance defined as P < 0.05.
Results: After propensity score matching, 47,894 patients were included in both the SGLT2 inhibitor and control cohorts. The incidence of new-onset HF was higher in the SGLT2 inhibitor group compared with controls (2.96% vs. 1.32%), with increased risk for both HFrEF (2.27% vs. 0.57%) and HFpEF (1.86% vs. 0.88%). Relative risks for new-onset HF, HFrEF, and HFpEF were 2.25 (95% CI), 3.96 (95% CI), and 2.11 (95% CI), respectively. In a subgroup excluding patients with prior T2DM (n=8,657), relative risks further increased to 8.73, 14.39, and 5.55, respectively.
Discussion: Our findings suggest that SGLT2 inhibitors may not confer the same cardioprotective effects in patients with ESRD or those undergoing dialysis as seen in earlier-stage CKD populations. This reduced efficacy may be attributed to diminished glomerular filtration rate and tubular function, both of which are essential for the diuretic and natriuretic mechanisms that contribute to SGLT2 inhibitors’ benefits. Prior studies, including DAPA-CKD and EMPA-KIDNEY, demonstrated mixed results on HF outcomes in patients with advanced kidney disease. These results raise caution regarding the generalized use of SGLT2 inhibitors in patients with advanced kidney dysfunction.
Conclusion: This study demonstrates a higher incidence of new onset heart failure, HFrEF, and HFpEF in patients with ESRD or on dialysis who are treated with SGLT2 inhibitors compared to matched controls.