Skip to main content
Erschienen in: Cardiovascular Drugs and Therapy 5/2021

19.10.2020 | 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

verfasst von: Alberto Aimo, Konstantinos Pateras, Kimon Stamatelopoulos, Antoni Bayes-Genis, Carlo Mario Lombardi, Claudio Passino, Michele Emdin, Georgios Georgiopoulos

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 5/2021

Einloggen, um Zugang zu erhalten

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
2.
Zurück zum Zitat McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004.CrossRef McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004.CrossRef
3.
Zurück zum Zitat Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129–200.CrossRef Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129–200.CrossRef
4.
Zurück zum Zitat Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136:e137–61.CrossRef Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136:e137–61.CrossRef
5.
Zurück zum Zitat Armstrong PW, Pieske B, Anstrom KJ, Ezekowitz J, Hernandez AF, Butler J, et al. Vericiguat in patients with heart failure and reduced ejection fraction. N Engl J Med. 2020;382:1883–93.CrossRef Armstrong PW, Pieske B, Anstrom KJ, Ezekowitz J, Hernandez AF, Butler J, et al. Vericiguat in patients with heart failure and reduced ejection fraction. N Engl J Med. 2020;382:1883–93.CrossRef
6.
Zurück zum Zitat McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, et al. DAPA-HF Trial Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381:1995–2008.CrossRef McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, et al. DAPA-HF Trial Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381:1995–2008.CrossRef
7.
Zurück zum Zitat Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Böhm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F. EMPEROR-reduced trial investigators. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413–1424. https://doi.org/10.1056/NEJMoa2022190. Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Böhm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F. EMPEROR-reduced trial investigators. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413–1424. https://​doi.​org/​10.​1056/​NEJMoa2022190.
8.
Zurück zum Zitat Volpe M, Carnovali M, Mastromarino V. The natriuretic peptides system in the pathophysiology of heart failure: from molecular basis to treatment. Clin Sci. 2016;130:57–77.CrossRef Volpe M, Carnovali M, Mastromarino V. The natriuretic peptides system in the pathophysiology of heart failure: from molecular basis to treatment. Clin Sci. 2016;130:57–77.CrossRef
9.
Zurück zum Zitat Bertero E, Prates Roma L, Ameri P, Maack C. Cardiac effects of SGLT2 inhibitors: the sodium hypothesis. Cardiovasc Res. 2018;114:12–8.CrossRef Bertero E, Prates Roma L, Ameri P, Maack C. Cardiac effects of SGLT2 inhibitors: the sodium hypothesis. Cardiovasc Res. 2018;114:12–8.CrossRef
10.
Zurück zum Zitat Verma S, Rawat S, Ho KL, Wagg CS, Zhang L, Teoh H, et al. Empagliflozin increases cardiac energy production in diabetes: novel translational insights into the heart failure benefits of SGLT2 inhibitors. JACC Basic Transl Sci. 2018;3:575–87.CrossRef Verma S, Rawat S, Ho KL, Wagg CS, Zhang L, Teoh H, et al. Empagliflozin increases cardiac energy production in diabetes: novel translational insights into the heart failure benefits of SGLT2 inhibitors. JACC Basic Transl Sci. 2018;3:575–87.CrossRef
11.
Zurück zum Zitat Zannad F, Ferreira JP, Pocock SJ, Anker SD, Butler J, Filippatos G, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet. 2020;396:819–29.CrossRef Zannad F, Ferreira JP, Pocock SJ, Anker SD, Butler J, Filippatos G, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet. 2020;396:819–29.CrossRef
13.
Zurück zum Zitat Lumley T. Network meta-analysis for indirect treatment comparisons. Stat Med. 2002;21:2313–24.CrossRef Lumley T. Network meta-analysis for indirect treatment comparisons. Stat Med. 2002;21:2313–24.CrossRef
14.
Zurück zum Zitat Caldwell DM, Ades AE, Higgins JP. Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ. 2005;331:897–900.CrossRef Caldwell DM, Ades AE, Higgins JP. Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ. 2005;331:897–900.CrossRef
15.
Zurück zum Zitat Li T, Puhan MA, Vedula SS, Singh S, Dickersin K. Network meta-analysis-highly attractive but more methodological research is needed. BMC Med. 2011;9:79.CrossRef Li T, Puhan MA, Vedula SS, Singh S, Dickersin K. Network meta-analysis-highly attractive but more methodological research is needed. BMC Med. 2011;9:79.CrossRef
16.
Zurück zum Zitat Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015;162:777–84.CrossRef Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015;162:777–84.CrossRef
17.
Zurück zum Zitat Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.CrossRef Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.CrossRef
18.
Zurück zum Zitat Guyatt GH, Oxman AD, Schünemann HJ, Tugwell P, Knottnerus A. GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology. J Clin Epidemiol. 2011;64:380–2.CrossRef Guyatt GH, Oxman AD, Schünemann HJ, Tugwell P, Knottnerus A. GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology. J Clin Epidemiol. 2011;64:380–2.CrossRef
19.
Zurück zum Zitat Jackson D, White IR, Riley RD. A matrix-based method of moments for fitting the multivariate random effects model for meta-analysis and meta-regression. Biom J. 2013;55:231–45.CrossRef Jackson D, White IR, Riley RD. A matrix-based method of moments for fitting the multivariate random effects model for meta-analysis and meta-regression. Biom J. 2013;55:231–45.CrossRef
20.
Zurück zum Zitat Spineli LM, Kalyvas C, Pateras K. Participants’ outcomes gone missing within a network of interventions: Bayesian modelling strategies. Stat Med. 2019;38:3861–79.CrossRef Spineli LM, Kalyvas C, Pateras K. Participants’ outcomes gone missing within a network of interventions: Bayesian modelling strategies. Stat Med. 2019;38:3861–79.CrossRef
21.
Zurück zum Zitat Gheorghiade M, Greene SJ, Butler J, Filippatos G, Lam CS, Maggioni AP, et al. Effect of vericiguat, a soluble guanylate cyclase stimulator, on natriuretic peptide levels in patients with worsening chronic heart failure and reduced ejection fraction: the SOCRATES-REDUCED randomized trial. JAMA. 2015;314:2251–62.CrossRef Gheorghiade M, Greene SJ, Butler J, Filippatos G, Lam CS, Maggioni AP, et al. Effect of vericiguat, a soluble guanylate cyclase stimulator, on natriuretic peptide levels in patients with worsening chronic heart failure and reduced ejection fraction: the SOCRATES-REDUCED randomized trial. JAMA. 2015;314:2251–62.CrossRef
22.
Zurück zum Zitat Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380:347–57.CrossRef Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380:347–57.CrossRef
23.
Zurück zum Zitat White IR, Barrett JK, Jackson D, Higgins JPT. Consistency and inconsistency in network meta-analysis: model estimation using multivariate meta-regression. Res Synth Methods. 2012;3:111–25.CrossRef White IR, Barrett JK, Jackson D, Higgins JPT. Consistency and inconsistency in network meta-analysis: model estimation using multivariate meta-regression. Res Synth Methods. 2012;3:111–25.CrossRef
24.
Zurück zum Zitat Salanti G. Indirect and mixed-treatment comparison, network, or multiple-treatments meta-analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool. Res Synth Methods. 2012;3:80–97.CrossRef Salanti G. Indirect and mixed-treatment comparison, network, or multiple-treatments meta-analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool. Res Synth Methods. 2012;3:80–97.CrossRef
25.
Zurück zum Zitat Chaimani A, Higgins JP, Mavridis D, Spyridonos P, Salanti G. Graphical tools for network meta-analysis in STATA. PLoS One. 2013;8:e76654.CrossRef Chaimani A, Higgins JP, Mavridis D, Spyridonos P, Salanti G. Graphical tools for network meta-analysis in STATA. PLoS One. 2013;8:e76654.CrossRef
26.
Zurück zum Zitat Cannon CP, Pratley R, Dagogo-Jack S, Mancuso J, Huyck S, Masiukiewicz U, Charbonnel B, Frederich R, Gallo S, Cosentino F, Shih WJ, Gantz I, Terra SG, Cherney DZI, McGuire DK; VERTIS CV Investigators. Cardiovascular outcomes with ertugliflozin in type 2 diabetes. N Engl J Med. 2020;383(15):1425–1435. https://doi.org/10.1056/NEJMoa2004967. Cannon CP, Pratley R, Dagogo-Jack S, Mancuso J, Huyck S, Masiukiewicz U, Charbonnel B, Frederich R, Gallo S, Cosentino F, Shih WJ, Gantz I, Terra SG, Cherney DZI, McGuire DK; VERTIS CV Investigators. Cardiovascular outcomes with ertugliflozin in type 2 diabetes. N Engl J Med. 2020;383(15):1425–1435. https://​doi.​org/​10.​1056/​NEJMoa2004967.
27.
Zurück zum Zitat Vardeny O, Miller R, Solomon SD. Combined neprilysin and renin-angiotensin system inhibition for the treatment of heart failure. JACC Heart Fail. 2014;2:663–70.CrossRef Vardeny O, Miller R, Solomon SD. Combined neprilysin and renin-angiotensin system inhibition for the treatment of heart failure. JACC Heart Fail. 2014;2:663–70.CrossRef
28.
Zurück zum Zitat D’Elia E, Iacovoni A, Vaduganathan M, Lorini FL, Perlini S, Senni M. Neprilysin inhibition in heart failure: mechanisms and substrates beyond modulating natriuretic peptides. Eur J Heart Fail. 2017;19:710–7.CrossRef D’Elia E, Iacovoni A, Vaduganathan M, Lorini FL, Perlini S, Senni M. Neprilysin inhibition in heart failure: mechanisms and substrates beyond modulating natriuretic peptides. Eur J Heart Fail. 2017;19:710–7.CrossRef
29.
Zurück zum Zitat Tamargo J. Sodium-glucose cotransporter 2 inhibitors in heart failure: potential mechanisms of action, adverse effects and future developments. Eur Cardiol. 2019;14:23–32.CrossRef Tamargo J. Sodium-glucose cotransporter 2 inhibitors in heart failure: potential mechanisms of action, adverse effects and future developments. Eur Cardiol. 2019;14:23–32.CrossRef
30.
Zurück zum Zitat Pieske B, Patel MJ, Westerhout CM, Anstrom KJ, Butler J, Ezekowitz J, et al. Baseline features of the VICTORIA (vericiguat global study in subjects with heart failure with reduced ejection fraction) trial. Eur J Heart Fail. 2019;21:1596–604.CrossRef Pieske B, Patel MJ, Westerhout CM, Anstrom KJ, Butler J, Ezekowitz J, et al. Baseline features of the VICTORIA (vericiguat global study in subjects with heart failure with reduced ejection fraction) trial. Eur J Heart Fail. 2019;21:1596–604.CrossRef
Metadaten
Titel
Relative Efficacy of Sacubitril-Valsartan, Vericiguat, and SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction: a Systematic Review and Network Meta-Analysis
verfasst von
Alberto Aimo
Konstantinos Pateras
Kimon Stamatelopoulos
Antoni Bayes-Genis
Carlo Mario Lombardi
Claudio Passino
Michele Emdin
Georgios Georgiopoulos
Publikationsdatum
19.10.2020
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 5/2021
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-020-07099-2

Weitere Artikel der Ausgabe 5/2021

Cardiovascular Drugs and Therapy 5/2021 Zur Ausgabe

„Übersichtlicher Wegweiser“: Lauterbachs umstrittener Klinik-Atlas ist online

17.05.2024 Klinik aktuell Nachrichten

Sie sei „ethisch geboten“, meint Gesundheitsminister Karl Lauterbach: mehr Transparenz über die Qualität von Klinikbehandlungen. Um sie abzubilden, lässt er gegen den Widerstand vieler Länder einen virtuellen Klinik-Atlas freischalten.

„Jeder Fall von plötzlichem Tod muss obduziert werden!“

17.05.2024 Plötzlicher Herztod Nachrichten

Ein signifikanter Anteil der Fälle von plötzlichem Herztod ist genetisch bedingt. Um ihre Verwandten vor diesem Schicksal zu bewahren, sollten jüngere Personen, die plötzlich unerwartet versterben, ausnahmslos einer Autopsie unterzogen werden.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Schlechtere Vorhofflimmern-Prognose bei kleinem linken Ventrikel

17.05.2024 Vorhofflimmern Nachrichten

Nicht nur ein vergrößerter, sondern auch ein kleiner linker Ventrikel ist bei Vorhofflimmern mit einer erhöhten Komplikationsrate assoziiert. Der Zusammenhang besteht nach Daten aus China unabhängig von anderen Risikofaktoren.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.