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SGLT2 Inhibitors and Kidney and Cardiac Outcomes According to Estimated GFR and Albuminuria Levels: A Meta-analysis of Randomized Controlled Trials

RATIONALE & OBJECTIVE: There are few data on the absolute effects of sodium/glucose cotransporter 2 (SGLT2) inhibitors, despite their importance in treatment decision making. We investigated absolute treatment effects according to baseline kidney disease status. STUDY DESIGN: Meta-analysis. STUD...

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Autores principales: Chun, Kwang Jin, Jung, Hae Hyuk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551546/
https://www.ncbi.nlm.nih.gov/pubmed/34746739
http://dx.doi.org/10.1016/j.xkme.2021.04.009
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author Chun, Kwang Jin
Jung, Hae Hyuk
author_facet Chun, Kwang Jin
Jung, Hae Hyuk
author_sort Chun, Kwang Jin
collection PubMed
description RATIONALE & OBJECTIVE: There are few data on the absolute effects of sodium/glucose cotransporter 2 (SGLT2) inhibitors, despite their importance in treatment decision making. We investigated absolute treatment effects according to baseline kidney disease status. STUDY DESIGN: Meta-analysis. STUDY POPULATIONS: Adults with type 2 diabetes, chronic kidney disease, or heart failure. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials of SGLT2 inhibitors (10 trials to November 20, 2020) for clinical outcomes of kidney disease progression, heart failure events, and major cardiovascular events. DATA EXTRACTION: Publications of 10 trials to November 20, 2020. ANALYTICAL APPROACH: The incidence rate difference (IRD) between SGLT2 inhibitor and placebo was compared across estimated glomerular filtration rate (eGFR) or urinary albumin-creatinine ratio (UACR) subgroups. RESULTS: Subgroup analyses included data from seven trials (61,821 participants with diabetes or chronic kidney disease). SGLT2 inhibitor treatment, in eGFR subgroups of <45, 45 to <60, and ≥60 mL/min/1.73 m(2), reduced 16.0, 9.5, and 1.9 heart failure events per 1,000 patient-year, respectively (P < 0.001 for heterogeneity). In urine UACR subgroups of >300, 30 to 300, and <30 mg/g, SGLT2 inhibitors reduced 17.3, 1.4, and 2.2 kidney disease events per 1,000 patient-year, respectively (P < 0.001 for heterogeneity), and 14.8, 8.7, and 2.1 heart failure events per 1,000 patient-year, respectively (P = 0.006 for heterogeneity). The pooled IRDs for major cardiovascular events were also greater in lower eGFR or overt albuminuria subgroups. In secondary analyses, risk differences calculated using pooled baseline and relative risks were comparable to the pooled IRDs, while the relative risk reductions for kidney and heart failure outcomes were consistent across the subgroups. For treatment-related harms, IRDs were similar between eGFR subgroups. LIMITATIONS: Study-level data rather than individual patient data were used. CONCLUSIONS: SGLT2 inhibitor treatment resulted in greater reductions of cardiovascular events in patients with lower eGFR and higher albuminuria and had substantially greater absolute benefits of renoprotection in patients with overt albuminuria than in their counterparts.
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spelling pubmed-85515462021-11-04 SGLT2 Inhibitors and Kidney and Cardiac Outcomes According to Estimated GFR and Albuminuria Levels: A Meta-analysis of Randomized Controlled Trials Chun, Kwang Jin Jung, Hae Hyuk Kidney Med Original Research RATIONALE & OBJECTIVE: There are few data on the absolute effects of sodium/glucose cotransporter 2 (SGLT2) inhibitors, despite their importance in treatment decision making. We investigated absolute treatment effects according to baseline kidney disease status. STUDY DESIGN: Meta-analysis. STUDY POPULATIONS: Adults with type 2 diabetes, chronic kidney disease, or heart failure. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials of SGLT2 inhibitors (10 trials to November 20, 2020) for clinical outcomes of kidney disease progression, heart failure events, and major cardiovascular events. DATA EXTRACTION: Publications of 10 trials to November 20, 2020. ANALYTICAL APPROACH: The incidence rate difference (IRD) between SGLT2 inhibitor and placebo was compared across estimated glomerular filtration rate (eGFR) or urinary albumin-creatinine ratio (UACR) subgroups. RESULTS: Subgroup analyses included data from seven trials (61,821 participants with diabetes or chronic kidney disease). SGLT2 inhibitor treatment, in eGFR subgroups of <45, 45 to <60, and ≥60 mL/min/1.73 m(2), reduced 16.0, 9.5, and 1.9 heart failure events per 1,000 patient-year, respectively (P < 0.001 for heterogeneity). In urine UACR subgroups of >300, 30 to 300, and <30 mg/g, SGLT2 inhibitors reduced 17.3, 1.4, and 2.2 kidney disease events per 1,000 patient-year, respectively (P < 0.001 for heterogeneity), and 14.8, 8.7, and 2.1 heart failure events per 1,000 patient-year, respectively (P = 0.006 for heterogeneity). The pooled IRDs for major cardiovascular events were also greater in lower eGFR or overt albuminuria subgroups. In secondary analyses, risk differences calculated using pooled baseline and relative risks were comparable to the pooled IRDs, while the relative risk reductions for kidney and heart failure outcomes were consistent across the subgroups. For treatment-related harms, IRDs were similar between eGFR subgroups. LIMITATIONS: Study-level data rather than individual patient data were used. CONCLUSIONS: SGLT2 inhibitor treatment resulted in greater reductions of cardiovascular events in patients with lower eGFR and higher albuminuria and had substantially greater absolute benefits of renoprotection in patients with overt albuminuria than in their counterparts. Elsevier 2021-06-19 /pmc/articles/PMC8551546/ /pubmed/34746739 http://dx.doi.org/10.1016/j.xkme.2021.04.009 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Chun, Kwang Jin
Jung, Hae Hyuk
SGLT2 Inhibitors and Kidney and Cardiac Outcomes According to Estimated GFR and Albuminuria Levels: A Meta-analysis of Randomized Controlled Trials
title SGLT2 Inhibitors and Kidney and Cardiac Outcomes According to Estimated GFR and Albuminuria Levels: A Meta-analysis of Randomized Controlled Trials
title_full SGLT2 Inhibitors and Kidney and Cardiac Outcomes According to Estimated GFR and Albuminuria Levels: A Meta-analysis of Randomized Controlled Trials
title_fullStr SGLT2 Inhibitors and Kidney and Cardiac Outcomes According to Estimated GFR and Albuminuria Levels: A Meta-analysis of Randomized Controlled Trials
title_full_unstemmed SGLT2 Inhibitors and Kidney and Cardiac Outcomes According to Estimated GFR and Albuminuria Levels: A Meta-analysis of Randomized Controlled Trials
title_short SGLT2 Inhibitors and Kidney and Cardiac Outcomes According to Estimated GFR and Albuminuria Levels: A Meta-analysis of Randomized Controlled Trials
title_sort sglt2 inhibitors and kidney and cardiac outcomes according to estimated gfr and albuminuria levels: a meta-analysis of randomized controlled trials
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551546/
https://www.ncbi.nlm.nih.gov/pubmed/34746739
http://dx.doi.org/10.1016/j.xkme.2021.04.009
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