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SGLT-2 Inhibitors and Cardiovascular Risk: An Analysis of CVD-REAL.

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posted on 2020-04-28, 11:51 authored by MA Cavender, A Norhammar, KI Birkeland, ME Jørgensen, JP Wilding, K Khunti, AZ Fu, J Bodegård, BT Blak, E Wittbrodt, M Thuresson, P Fenici, N Hammar, M Kosiborod, CVD-REAL Investigators and Study Group
BACKGROUND: Prior studies found patients treated with sodium-glucose co-transporter-2 inhibitors (SGLT-2i) had lower rates of death and heart failure (HF). Whether the benefits of SGLT-2i vary based upon the presence of cardiovascular disease (CVD) is unknown. OBJECTIVES: This study sought to determine the association between initiation of SGLT-2i therapy and HF or death in patients with and without CVD. METHODS: The CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) study was a multinational, observational study in which adults with type 2 diabetes were identified. Patients prescribed an SGLT-2i or other glucose-lowering drugs (GLDs) were matched based on a propensity score for initiation of an SGLT-2i. Hazard ratios (HRs) for the risk of death, HF, and HF or death in patients with and without established CVD were estimated for each country and pooled. RESULTS: After propensity score matching, 153,078 patients were included in each group. At baseline, 13% had established CVD. Compared with therapy using other GLDs, initiation of an SGLT-2i was associated with lower risk of death in patients with and without CVD (HR: 0.56; 95% confidence interval [CI]: 0.44 to 0.70; and HR: 0.56; 95% CI: 0.50 to 0.63, respectively). There were also associations between SGLT-2i and lower risk of HF (HR: 0.72; 95% CI: 0.63 to 0.82; and HR: 0.61; 95% CI: 0.48 to 0.78, respectively) and the composite of HF or death (HR: 0.63; 95% CI: 0.57 to 0.70; and HR: 0.56; 95% CI: 0.50 to 0.62, respectively) observed in patients with and without established CVD. CONCLUSIONS: In this large, multinational, observational study, initiation of SGLT-2i was associated with lower risk of death and HF regardless of pre-existing CVD. Ongoing clinical trials will provide further evidence regarding the benefit of SGLT-2i in patients without established CVD. (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors [CVD-REAL]; NCT02993614).


Data from Norway were obtained from the Norwegian Cause of Death Registry, the Norwegian Patient Registry, and the Norwegian Prescription Registry. The interpretation and reporting of these data were the sole responsibilities of the authors, and no endorsement by the Norwegian patient register was intended nor should be inferred. This study is based in part on data from the Clinical Practice Research Datalink (CPRD) obtained under license from the U.K. Medicines and Healthcare Products Regulatory Agency. Data were provided by patients and collected by the National Health Service as part of patient care and support. This CPRD study also used data from the Office for National Statistics and Hospital Episode Statistics (with permission from the Health and Social Care Information Centre).The study was approved by the Independent Scientific Advisory Committee of the CPRD (protocol16_064RAR). The Health Improvement Network data from the U.K. were also used, and the independent Scientific Review Committee approved the study(protocol 16THIN027A1). The interpretation and conclusions contained in this study are those of the authors alone. Editorial support was provided by Nicola Truss, PhD, in Science Communications, Springer Healthcare, and funded by AstraZeneca.



Journal of the American College of Cardiology, 2018, 71 (22), pp. 2497-2506

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Journal of the American College of Cardiology








Elsevier for American College of Cardiology



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