Relative Efficacy of Sacubitril-Valsartan, Vericiguat, and SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction: a Systematic Review and Network Meta-Analysis

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.

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Abbreviations

ACEi/ARB:

Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker

CI:

Confidence interval

CV:

Cardiovascular

HFrEF:

Heart failure with reduced ejection fraction

HR:

Hazard ratio

MRA:

Mineralocorticoid receptor antagonist

NMA:

Network meta-analysis

NP:

Natriuretic peptide

RCT:

Randomized controlled trial

SOC:

Standard-of-care

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Correspondence to Alberto Aimo.

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Conflict of Interest

M.E. is one of the 2 Italian national leaders of the VICTORIA trial; the other authors have no conflicts of interest to disclose.

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Aimo, A., Pateras, K., Stamatelopoulos, K. et al. Relative Efficacy of Sacubitril-Valsartan, Vericiguat, and SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction: a Systematic Review and Network Meta-Analysis. Cardiovasc Drugs Ther (2020). https://doi.org/10.1007/s10557-020-07099-2

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Keywords

  • Heart failure
  • Sacubitril/valsartan
  • Vericiguat
  • SGLT2-inhibitors
  • Efficacy
  • Network meta-analysis