Relative Efficacy of Sacubitril-Valsartan, Vericiguat, and SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction: a Systematic Review and Network Meta-Analysis
Aimo, Alberto; Pateras, Konstantinos; Stamatelopoulos, Kimon; Bayes-Genis, Antoni; Lombardi, Carlo Mario; Passino, Claudio; Emdin, Michele; Georgiopoulos, Georgios
(2021) Cardiovascular Drugs and Therapy, volume 35, issue 5, pp. 1067 - 1076
(Article)
Abstract
BACKGROUND: Sacubitril/valsartan, vericiguat, and the sodium-glucose co-transporter-2 inhibitors (SGLT2i) dapagliflozin and empagliflozin proved effective in phase 3 trials on heart failure with reduced ejection fraction (HFrEF). METHODS: We compared the treatment arms (sacubitril/valsartan, vericiguat, and SGLT2i) with the respective control arms (standard-of-care [SOC]) through a network meta-analysis of the phase
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3 trials (PARADIGM-HF, VICTORIA, DAPA-HF, EMPEROR-Reduced), a phase 2 trial on vericiguat and the HFrEF subgroup of DECLARE-TIMI 58. RESULTS: There was a trend towards decreased risk of cardiovascular (CV) death or HF hospitalization with SGLT2i than sacubitril/valsartan (HR 0.92, 95% CI 0.81 to 1.05) and vericiguat (HR 0.83, 95% CI 0.73 to 0.94). A non-significant effect of SGLT2i on CV mortality compared to sacubitril/valsartan (HR 1.04, 95% CI 0.88 to 1.24) and vericiguat (HR 0.88, 95% CI 0.63 to 1.22) was found. SGLT2i demonstrated the greatest effect on HF hospitalization (HR 0.69, 95% CI 0.62 to 0.77) over the SOC, as well as a significant benefit over vericiguat (HR 0.77, 95% CI 0.66 to 0.89), but not over sacubitril/valsartan (HR 0.87, 95% CI 0.75 to 1.02). SGLT2i were ranked as the most effective therapy, followed by sacubitril/valsartan and vericiguat. CONCLUSIONS: Based on an indirect comparison, SGLT2i therapy is not associated with a significantly lower risk of CV death or HF hospitalization or CV death alone compared to sacubitril/valsartan or vericiguat. The risk of HF hospitalization does not differ significantly between patients on SGLT2i or sacubitril/valsartan, while dapagliflozin is superior to vericiguat. REGISTRATION NUMBER: PROSPERO ID 186351.
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Keywords: Efficacy, Heart failure, Network meta-analysis, Sacubitril/valsartan, SGLT2-inhibitors, Vericiguat, Cardiology and Cardiovascular Medicine, Pharmacology (medical), Pharmacology, Review, Journal Article
ISSN: 0920-3206
Publisher: Kluwer Academic Publishers
Note: Publisher Copyright: © 2020, Springer Science+Business Media, LLC, part of Springer Nature. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
(Peer reviewed)