# Impact of the angiotensin receptor-neprilysin inhibitor on chronic heart failure due to adult congenital heart disease: A systematic review and meta-analysis

**Authors:** Bibhuti B. Das, Shriprasad Deshpande, Lazaros Nikolaidis, Jianli Niu

PMC · DOI: 10.1016/j.jhlto.2025.100230 · JHLT Open · 2025-02-18

## TL;DR

This study reviews and analyzes the effects of a new heart failure drug on adults with congenital heart disease, finding it improves function but requires caution due to side effects.

## Contribution

The study is the first systematic review and meta-analysis evaluating ARNIs specifically in adults with congenital heart disease.

## Key findings

- ARNIs significantly improved NYHA functional class compared to ACEIs/ARBs.
- ARNI therapy reduced systolic blood pressure but increased serum creatinine levels.
- No significant change in serum potassium levels was observed with ARNI use.

## Abstract

Heart failure (HF) is a significant complication in adults with congenital heart disease (ACHD), often requiring advanced therapeutic strategies. Angiotensin receptor-neprilysin inhibitors (ARNIs) have emerged as a promising alternative to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in HF management. However, their safety and efficacy in ACHD-related HF remain unclear. This systematic review and meta-analysis aim to evaluate the impact of ARNIs on functional and safety outcomes in this unique patient population.

We conducted a systematic review and meta-analysis of published studies assessing the use of ARNIs in ACHD patients with HF, comparing them to ACEIs/ARBs. The primary outcome was the change in New York Heart Association (NYHA) functional class (FC). Additionally, we assessed the safety profile of ARNIs in this population.

Our meta-analysis included 14 studies encompassing 305 patients. Substituting ACEIs/ARBs with ARNIs significantly improved the NYHA functional class (log odds ratio [log OR] 0.67, 95% CI 0.15–1.19; p = 0.01). ARNI therapy was associated with a notable reduction in systolic blood pressure (mean difference [MD] -0.49, 95% CI -0.70 to -0.29, p < 0.001) and an increase in serum creatinine levels (MD 0.30, 95% CI 0.10–0.49, p < 0.001). However, no significant change in serum potassium levels was observed (MD 0.00, 95% CI -0.61–0.61, p = 0.99).

The addition of ARNIs to standard HF therapy may enhance functional outcomes in ACHD patients. However, the increased risk of hypotension and elevated serum creatinine levels necessitates careful monitoring. Further research is essential to better define the role of ARNIs in managing ACHD-related HF.

URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42024591442.

## Linked entities

- **Diseases:** heart failure (MONDO:0005252)

## Full-text entities

- **Diseases:** HF (MESH:D006333), ACHD (MESH:D006330), hypotension (MESH:D007022)
- **Chemicals:** ARNI (-), potassium (MESH:D011188), creatinine (MESH:D003404)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

52 references — full list in the complete paper: https://tomesphere.com/paper/PMC12142544/full.md

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Source: https://tomesphere.com/paper/PMC12142544