Differences in outcomes of hospitalizations for heart failure after SGLT2 inhibitor treatment: effect modification by atherosclerotic cardiovascular disease

Cardiovasc Diabetol. 2021 Oct 23;20(1):213. doi: 10.1186/s12933-021-01406-3.

Abstract

Background: The treatment effects on hospitalization for heart failure (hHF) from sodium-glucose cotransporter 2 (SGLT2) inhibitors may vary among type 2 diabetes (T2D) patients depending on whether or not they have established atherosclerotic cardiovascular diseases (ASCVD). We aimed to examine differences in hHF outcomes after dapagliflozin or empagliflozin use between T2D patients with and without a history of established ASCVD.

Methods: We conducted a retrospective multi-institutional cohort study in Taiwan. We included T2D patients newly receiving dapagliflozin or empagliflozin during 2016-2019, and followed them up until December 31, 2020. We implemented 1:1 propensity score matching to create homogenous groups for comparisons. We generated Cox proportional hazard models to compare the risk of hHF between dapagliflozin and empagliflozin (reference group). We included interaction terms of SGLT2 inhibitor and ASCVD history in the regression models to examine effect modification by ASCVD.

Results: We included a total cohort of 9,586 dapagliflozin new users and 9,586 matched empagliflozin new users. The overall hHF risks were similar for dapagliflozin and empagliflozin (HR: 0.90, 95% CI 0.74-1.09). However, differential hHF risks between dapagliflozin and empagliflozin were observed only in the subgroup without ASCVD (HR: 0.67, 95% CI 0.49-0.90), while not in the subgroup with ASCVD (HR: 1.12, 95% 0.87-1.45), and the p-value for examining interaction was 0.0097.

Conclusion: In this study, history of established ASCVD was associated with different hHF risks among SGLT2 inhibitors. For T2D patients without ASCVD, dapagliflozin may offer a more favorable hHF reduction effect, compared to empagliflozin, in clinical practice. Future prospective studies should be conducted to validate our findings.

Keywords: Anti-diabetic drugs; Atherosclerotic cardiovascular diseases; Effect modification; Hospitalization for heart failure; Sodium-glucose cotransporter 2 inhibitors.

Publication types

  • Comparative Study
  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atherosclerosis / diagnosis
  • Atherosclerosis / epidemiology*
  • Benzhydryl Compounds / adverse effects
  • Benzhydryl Compounds / therapeutic use*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Female
  • Glucosides / adverse effects
  • Glucosides / therapeutic use*
  • Heart Failure / diagnosis
  • Heart Failure / epidemiology
  • Heart Failure / therapy*
  • Hospitalization*
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*
  • Taiwan / epidemiology
  • Time Factors
  • Treatment Outcome

Substances

  • Benzhydryl Compounds
  • Glucosides
  • Sodium-Glucose Transporter 2 Inhibitors
  • dapagliflozin
  • empagliflozin