Relative Efficacy of Sacubitril-Valsartan, Vericiguat, and SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fract
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REVIEW ARTICLE
Relative Efficacy of Sacubitril-Valsartan, Vericiguat, and SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction: a Systematic Review and Network Meta-Analysis Alberto Aimo 1,2 & Konstantinos Pateras 3 & Kimon Stamatelopoulos 4 & Antoni Bayes-Genis 5,6 & Carlo Mario Lombardi 7 & Claudio Passino 1,8 & Michele Emdin 1,8 & Georgios Georgiopoulos 4,9 Accepted: 11 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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 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. Keywords Heart failure . Sacubitril/valsartan . Vericiguat . SGLT2-inhibitors . Efficacy . Network meta-analysis
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10557-020-07099-2) contains supplementary material, which is available to authorized users. * Alberto Aimo [email protected]; [email protected]
5
Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
6
CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain
7
Department of Medical and Surgical Specialties, Radiological Sciences, Public Health University and Civil Hospital, Brescia, Italy
1
Institute of Life Sciences, Scuola Superiore Sant’Anna, Piazza Martiri della Libertà 33, 56124 Pisa, Italy
2
Cardiology Division, University Hospital of Pisa, Piazza Martiri della Libertà 33, 56124 Pisa, Italy
3
Department of Biostatis
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