Yao Hao Teo1, Celine Shuen Yin Yoong1, Nicholas L Syn1, Yao Neng Teo1, Jia Yang Alex Cheong1, Yoke-Ching Lim1,2, Chi-Hang Lee1,2, Tiong-Cheng Yeo1,2, Ping Chai1,2, Raymond C C Wong1,2, Weiqin Lin1,2, Ching-Hui Sia3,4. 1. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. 2. Department of Cardiology, National University Heart Centre Singapore, NUHS Tower Block Level 9, 1E Kent Ridge Road, Singapore, 119228, Singapore. 3. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. ching_hui_sia@nuhs.edu.sg. 4. Department of Cardiology, National University Heart Centre Singapore, NUHS Tower Block Level 9, 1E Kent Ridge Road, Singapore, 119228, Singapore. ching_hui_sia@nuhs.edu.sg.
Abstract
PURPOSE: Empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin have been shown in randomized controlled trials to improve cardiovascular, metabolic, and renal outcomes in heart failure patients. To date, there has not been any meta-analysis examining the differences in clinical outcomes across different SGLT2 inhibitors in heart failure patients. METHODS: Four electronic databases (PubMed, Embase, Cochrane, SCOPUS) were searched on 13 September 2020 for articles published from 1 January 2000 to 13 September 2020 examining the effect of SGLT2 inhibitors on cardiovascular, renal, and metabolic outcomes in heart failure patients. Frequentist network meta-analysis was performed on extracted data. RESULTS: Ten randomized controlled trials were included with a combined cohort of 15,373 patients. In heart failure patients, frequentist network meta-analysis demonstrated no demonstrable difference in treatment effect across the SGLT2 inhibitors for heart failure hospitalization, cardiovascular deaths, composite of cardiovascular deaths and heart failure hospitalizations, all-cause mortality, and a composite of cardiovascular deaths and non-fatal myocardial infarction and non-fatal stroke. There was no demonstrable difference in treatment effect for worsening renal function or the weighted mean difference for weight, hemoglobin A1c, and systolic blood pressure. CONCLUSIONS: There were no demonstrable treatment differences across SGLT2 inhibitors across cardiovascular, renal, and metabolic outcomes, although this needs to be interpreted considering the wide confidence intervals, limited number of included studies, and heterogeneity present. Future research of different SGLT2 inhibitors in head-to-head studies is warranted to determine if there is a drug class effect.
PURPOSE: Empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin have been shown in randomized controlled trials to improve cardiovascular, metabolic, and renal outcomes in heart failure patients. To date, there has not been any meta-analysis examining the differences in clinical outcomes across different SGLT2 inhibitors in heart failure patients. METHODS: Four electronic databases (PubMed, Embase, Cochrane, SCOPUS) were searched on 13 September 2020 for articles published from 1 January 2000 to 13 September 2020 examining the effect of SGLT2 inhibitors on cardiovascular, renal, and metabolic outcomes in heart failure patients. Frequentist network meta-analysis was performed on extracted data. RESULTS: Ten randomized controlled trials were included with a combined cohort of 15,373 patients. In heart failure patients, frequentist network meta-analysis demonstrated no demonstrable difference in treatment effect across the SGLT2 inhibitors for heart failure hospitalization, cardiovascular deaths, composite of cardiovascular deaths and heart failure hospitalizations, all-cause mortality, and a composite of cardiovascular deaths and non-fatal myocardial infarction and non-fatal stroke. There was no demonstrable difference in treatment effect for worsening renal function or the weighted mean difference for weight, hemoglobin A1c, and systolic blood pressure. CONCLUSIONS: There were no demonstrable treatment differences across SGLT2 inhibitors across cardiovascular, renal, and metabolic outcomes, although this needs to be interpreted considering the wide confidence intervals, limited number of included studies, and heterogeneity present. Future research of different SGLT2 inhibitors in head-to-head studies is warranted to determine if there is a drug class effect.
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