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Sacubitril/valsartan and arrhythmic burden in patients with heart failure and reduced ejection fraction: a systematic review and meta-analysis

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Abstract

The aim of this study was to assess whether angiotensin receptor/neprilysin inhibitor (ARNI) decreases ventricular arrhythmic burden compared to angiotensin-converting enzyme inhibitors or angiotensin receptor antagonist (ACE-I/ARB) treatment in chronic heart failure with reduced ejection fraction (HFrEF) patients. Further, we assessed if ARNI influenced the percentage of biventricular pacing. A systematic review of studies (both RCTs and observational studies) including HFrEF patients and those receiving ARNI after ACE-I/ARB treatment was conducted using Medline and Embase up to February 2023. Initial search found 617 articles. After duplicate removal and text check, 1 RCT and 3 non-RCTs with a total of 8837 patients were included in the final analysis. ARNI was associated with a significative reduction of ventricular arrhythmias both in RCT (RR 0.78 (95% CI 0.63–0.96); p = 0.02) and observational studies (RR 0.62; 95% CI 0.53–0.72; p < 0.001). Furthermore, in non-RCTs, ARNI also reduced sustained (RR 0.36 (95% CI 0.2–0.63); p < 0.001), non-sustained VT (RR 0.67 (95% CI 0.57–0.80; p = 0.007), ICD shock (RR 0.24 (95% CI 0.12–0.48; p < 0.001), and increased biventricular pacing (2.96% (95% CI 2.25–3.67), p < 0.001). In patients with chronic HFrEF, switching from ACE-I/ARB to ARNI treatment was associated with a consistent reduction of ventricular arrhythmic burden. This association could be related to a direct pharmacological effect of ARNI on cardiac remodeling.

Trial registration: CRD42021257977.

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Author information

Authors and Affiliations

  1. Cardiology Department, Valduce Hospital, Como, Italy

    A. Pozzi & G. Corrado

  2. Cardiology Department, Papa Giovanni XXIII Hospital, Bergamo, Italy

    R. Abete, A. Iorio & A. Iacovoni

  3. Ospedale di Circolo Busto Arsizio, Busto Arsizio, Italy

    E. Tavano

  4. Cardiology Department, Rigshospitalet University Hospital, Copenhagen, Denmark

    S. L. Kristensen

  5. Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy

    F. Rea

  6. Cardiology Department, Southmead Hospital, Bristol, UK

    C. Wong

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Contributions

All authors read and approved the final manuscript. Study conceptualization: Andrea Pozzi, Raffaele Abete, Elisa Tavano, Søren Lund Kristensen, Federico Rea, Annamaria Iorio, Attilio Iacovoni, Giovanni Corrado, and Chich Wong. Data source: Andrea Pozzi, Raffaele Abete, Elisa Tavano, and Federico Rea. Statistical analysis: Federico Rea and Andrea Pozzi. Draft the paper: Andrea Pozzi, Raffaele Abete, Elisa Tavano, Søren Lund Kristensen, and Chich Wong. Critical revision: Annamaria Iorio, Attilio Iacovoni, and Giovanni Corrado.

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Correspondence to A. Pozzi.

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Pozzi, A., Abete, R., Tavano, E. et al. Sacubitril/valsartan and arrhythmic burden in patients with heart failure and reduced ejection fraction: a systematic review and meta-analysis. Heart Fail Rev 28, 1395–1403 (2023). https://doi.org/10.1007/s10741-023-10326-1

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