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Sacubitril/valsartan compared to equivalent/sub-equivalent dose angiotensin receptor blocker or angiotensin-converting enzyme inhibitor in heart failure with reduced ejection fraction: a meta-analysis of randomized trials

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Abstract

Purpose

The objective of this meta-analysis is to determine how sacubitril/valsartan (SV) compares to equivalent and sub-equivalent angiotensin receptor blockers (ARB) or angiotensin-converting enzyme inhibitors (ACEI) in patients with heart failure with reduced ejection fraction (HFrEF).

Methods

The databases of PubMed and EMBASE were used to identify those randomized controlled trials which compared SV to ARB/ACEI in patients with HFrEF. Only those trials that reported outcomes regarding total mortality, cardiovascular mortality, and worsening heart failure were considered. Meta-analysis was performed separately in those patients receiving equivalent doses of ARB/ACEI and those receiving sub-equivalent doses. Equivalent doses were SV 97/103 = valsartan 160 mg twice daily = enalapril 20 mg twice daily = ramipril 5 mg twice daily. Meta-analyses were performed using Review Manager 5.4.

Results

Twelve randomized trials were identified involving 17,484 patients: 11,291 in the sub-equivalent group (8 trials) and 6193 in the equivalent group (4 trials). Meta-analyses showed there were no statistical differences regarding the outcomes of total mortality, cardiovascular mortality, and worsening heart failure in the equivalent dosing group. However, SV reduced total mortality (risk ratio (RR) = 0.85, 95% confidence interval (CI) = 0.78–0.93, p < 0.001), cardiovascular mortality (RR = 0.81, 95% CI = 0.73–0.90, p ≤ 0.001) and worsening heart failure (RR = 0.77, 95% CI = 0.64–0.92, p = 0.005) in the sub-equivalent group.

Conclusion

When compared to equivalent doses of ARB/ACEI, SV is not superior in reducing mortality and worsening heart failure. SV is superior when compared to sub-equivalent doses of ACEI.

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Data availability

Clinical trial data were extracted from published studies in the PubMed and EMBASE databases. Data from the statistical analyses are included in the manuscript text and figures.

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Authors and Affiliations

  1. Heart Failure Program, Northern Arizona VA Health Care System, 500 N Hwy 89, Prescott, AZ, 86313, USA

    Joseph P. Rindone

  2. Southern Arizona VA Health Care System, 3601 S. 6th Ave, Tucson, AZ, 85723, USA

    Chadwick K. Mellen

Authors
  1. Joseph P. Rindone
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Contributions

JPR was involved in the conception, research, and writing of this manuscript. CKM was involved in the research and review of this manuscript.

Corresponding author

Correspondence to Joseph P. Rindone.

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Ethical approval

Since this was a meta-analysis and individual human subjects were not involved, this study was exempted from needing approval by our local IRB or R&D committee.

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This study is a meta-analysis, and individual human subjects were not included, so consent was not needed.

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The authors declare no competing interests.

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Rindone, J.P., Mellen, C.K. Sacubitril/valsartan compared to equivalent/sub-equivalent dose angiotensin receptor blocker or angiotensin-converting enzyme inhibitor in heart failure with reduced ejection fraction: a meta-analysis of randomized trials. Eur J Clin Pharmacol (2024). https://doi.org/10.1007/s00228-024-03686-6

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