TY - JOUR
T1 - Cardiovascular outcomes with sodium–glucose cotransporter-2 inhibitors vs other glucose-lowering drugs in 13 countries across three continents
T2 - analysis of CVD-REAL data
AU - Khunti, Kamlesh
AU - Kosiborod, Mikhail
AU - Kim, Dae Jung
AU - Kohsaka, Shun
AU - Lam, Carolyn S.P.
AU - Goh, Su Yen
AU - Chiang, Chern En
AU - Shaw, Jonathan E.
AU - Cavender, Matthew A.
AU - Tangri, Navdeep
AU - Franch-Nadal, Josep
AU - Holl, Reinhard W.
AU - Jørgensen, Marit E.
AU - Norhammar, Anna
AU - Eriksson, Johan G.
AU - Zaccardi, Francesco
AU - Karasik, Avraham
AU - Magliano, Dianna J.
AU - Thuresson, Marcus
AU - Chen, Hungta
AU - Wittbrodt, Eric T.
AU - Bodegård, Johan
AU - Surmont, Filip
AU - Fenici, Peter
AU - on behalf of the CVD-REAL Investigators and Study Group
N1 - Funding Information:
MEJ is a shareholder of Novo Nordisk. MEJ has received grants from AstraZeneca, Amgen, Boehringer Ingelheim and Sanofi Aventis.
Funding Information:
The authors acknowledge Kevin Kennedy (Saint Luke's Mid America Heart Institute) for his independent validation of the meta analyses. Fabian Hoti, Solomon Christopher and Minna Vehkala (StatFinn & EPID Research, Espoo, Finland) and Bendix Carstensen (Diabetes Center, Gentofte, Denmark) are all acknowledged for database management and statistical work. Data from the Norwegian Patient Register have been used in this publication. The interpretation and reporting of these data are the sole responsibility of the authors, and no endorsement by the Norwegian patient register is intended nor should be inferred. KK is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration East Midlands (ARC EM) and the NIHR Leicester Biomedical Research Centre (BRC). Editorial support in styling, formatting and submission of the manuscript was provided by Nicola Truss, PhD, inScience Communications, Springer Healthcare Ltd, UK, and funded by AstraZeneca.
Funding Information:
NT has received consulting fees from Otsuka, Tricida, BI-Lilly, Janssen and AstraZeneca. He has received research support from AstraZeneca, Otsuka and Janssen, including for this work. He owns stock in Tricida, Pulsedata, Mesentech and Renibus. His research program is supported by the Canadian Institute for Health Research and Research Manitoba.
Funding Information:
KK is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration East Midlands (ARC EM) and the NIHR Leicester Biomedical Research Centre (BRC).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Cardiovascular outcomes
KW - Heart failure
KW - Sodium–glucose cotransporter-2 inhibitors
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85112263464&partnerID=8YFLogxK
U2 - 10.1186/s12933-021-01345-z
DO - 10.1186/s12933-021-01345-z
M3 - Article
C2 - 34332558
AN - SCOPUS:85112263464
SN - 1475-2840
VL - 20
JO - Cardiovascular Diabetology
JF - Cardiovascular Diabetology
IS - 1
M1 - 159
ER -
