Cardiovascular Diabetology (Jul 2021)

Cardiovascular outcomes with sodium–glucose cotransporter-2 inhibitors vs other glucose-lowering drugs in 13 countries across three continents: analysis of CVD-REAL data

  • Kamlesh Khunti,
  • Mikhail Kosiborod,
  • Dae Jung Kim,
  • Shun Kohsaka,
  • Carolyn S. P. Lam,
  • Su-Yen Goh,
  • Chern-En Chiang,
  • Jonathan E. Shaw,
  • Matthew A. Cavender,
  • Navdeep Tangri,
  • Josep Franch-Nadal,
  • Reinhard W. Holl,
  • Marit E. Jørgensen,
  • Anna Norhammar,
  • Johan G. Eriksson,
  • Francesco Zaccardi,
  • Avraham Karasik,
  • Dianna J. Magliano,
  • Marcus Thuresson,
  • Hungta Chen,
  • Eric Wittbrodt,
  • Johan Bodegård,
  • Filip Surmont,
  • Peter Fenici,
  • the CVD-REAL Investigators and Study Group

DOI
https://doi.org/10.1186/s12933-021-01345-z
Journal volume & issue
Vol. 20, no. 1
pp. 1 – 15

Abstract

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Abstract Background Randomized, controlled cardiovascular outcome trials may not be fully representative of the management of patients with type 2 diabetes across different geographic regions. We conducted analyses of data from the multinational CVD-REAL consortium to determine the association between initiation of sodium–glucose cotransporter-2 inhibitors (SGLT-2i) and cardiovascular outcomes, including subgroup analyses based on patient characteristics. Methods De-identified health records from 13 countries across three continents were used to identify patients newly-initiated on SGLT-2i or other glucose-lowering drugs (oGLDs). Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching for oGLD initiation. In the matched groups hazard ratios (HRs) for hospitalization for heart failure (HHF), all-cause death (ACD), the composite of HHF or ACD, myocardial infarction (MI) and stroke were estimated by country, and pooled using a weighted meta-analysis. Multiple subgroup analyses were conducted across patient demographic and clinical characteristics to examine any heterogeneity in treatment effects. Results Following matching, 440,599 new users of SGLT-2i and oGLDs were included in each group. Mean follow-up time was 396 days for SGLT-2i initiation and 406 days for oGLDs initiation. SGLT-2i initiation was associated with a lower risk of HHF (HR: 0.66, 95%CI 0.58–0.75; p < 0.001), ACD (HR: 0.52, 95%CI 0.45–0.60; p < 0.001), the composite of HHF or ACD (HR: 0.60, 95%CI 0.53–0.68; p < 0.001), MI (HR: 0.85, 95%CI 0.78–0.92; p < 0.001), and stroke (HR: 0.78, 95%CI 0.72–0.85; p < 0.001); regardless of patient characteristics, including established cardiovascular disease, or geographic region. Conclusions This CVD-REAL study extends the findings from the SGLT-2i clinical trials to the broader setting of an ethnically and geographically diverse population, and across multiple subgroups. Trial registration NCT02993614

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