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Central sleep apnea treatment in patients with heart failure with reduced ejection fraction: a network meta-analysis

  • Sleep Breathing Physiology and Disorders • Original Article
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Abstract

Purpose

Adaptive servo-ventilation (ASV) is contraindicated for the treatment of central sleep apnea (CSA) in patients with heart failure with reduced ejection fraction (HFrEF), limiting treatment options. Though continuous positive airway pressure (CPAP), bi-level PAP with back-up rate (BPAP-BUR), and transvenous phrenic nerve stimulation (TPNS) are alternatives, not much is known about their comparative efficacies, which formed the basis of conducting this network meta-analysis. We sought to analyze their comparative effectiveness in reducing apnea hypopnea index (AHI). Additionally, we also studied their comparative effectiveness on subjective daytime sleepiness as assessed by Epworth sleepiness score (ESS).

Methods

Randomized controlled trials (RCTs) from PubMed were analyzed in a network meta-analysis and relative superiority was computed based on P-score ranking and Hasse diagrams.

Results

Network meta-analysis based on 8 RCTs showed that when compared to guideline-directed medical therapy (GDMT—used as a common comparator across trials), reduction in AHI by ASV (− 26.05 [− 38.80; − 13.31]), TPNS (− 24.90 [− 42.88; − 6.92]), BPAP-BUR (− 20.36 [− 36.47; − 4.25]), and CPAP (− 16.01 [− 25.42; − 6.60]) were statistically significant but not between the interventions. Based on 6 RCTs of all the interventions, only TPNS showed a statistically significant decrease in ESS (− 3.70 (− 5.58; − 1.82)) when compared to GDMT, while also showing significant differences when compared with ASV (− 3.20 (− 5.86; − 0.54)), BPAP-BUR (− 4.00 (− 7.33; − 0.68)), and CPAP (− 4.45 (− 7.75; − 1.14)). Ranking of treatments based on Hasse diagram, accounting for both AHI and ESS as outcomes for relative hierarchy showed relative superiority of both ASV and TPNS over BPAP-BUR and CPAP.

Conclusions

Results indicated relative superiority of TPNS and ASV to BPAP-BUR and CPAP in their effects on AHI and ESS.

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Availability of data and material

Available on reasonable request.

Code availability

Codes are provided in the Supplementary information.

This article does not contain any studies with human participants performed by any of the authors.

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Funding

This study was not sponsored by any funding agency or pharmaceutical company.

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Pulmonary, Allergy, Critical Care & Sleep Medicine, Emory University School of Medicine, 613 Michael St, NE, Atlanta, GA, 30322, USA

    Imran H. Iftikhar

  2. Atlanta Veterans Affairs Medical Center, Decatur, GA, 30033, USA

    Imran H. Iftikhar

  3. Department of Medicine, Division of Pulmonary Diseases and Critical Care Medicine, School of Medicine, University of California, Irvine, Irvine, CA, 92617, USA

    Rami N. Khayat

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  1. Imran H. Iftikhar
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Contributions

IHI had full access to all extracted data in the network meta-analysis and takes responsibility for the integrity of the data and the accuracy of the data analysis. IHI and RNK contributed to the assessment of study quality, the interpretation of analyses, and in revisions of the manuscript.

Corresponding author

Correspondence to Imran H. Iftikhar.

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Conflict of interest

IHI reports no conflicts of interest. RNK has received consulting fees in 2018 from Respicardia Inc, a company that manufactures a transvenous phrenic nerve stimulator; and consulting fees in 2020 from Philips Respironics, a company that manufactures positive airway pressure devices.

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Comments

Interesting network meta-analysis that studied the effectiveness of different treatments for central sleep apnoea in heart failure patients. Findings suggest that apart from adaptive servo-ventilation, transvenous phrenic nerve stimulation is an effective method to reduce apnoeic episodes in patents with CSA and heart failure. Given that adaptive servo ventilation has been shown to cause harm in HF patients, TPNS appears as a possible choice of treatment in HF. However, it must be stressed that clinical effectiveness as well as outcomes associated with TPNS is currently uncertain, thus stressing the need for RCTs using TPNS as the active comparator.

Tolga Guevenc

Istanbul, Turkey

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Iftikhar, I.H., Khayat, R.N. Central sleep apnea treatment in patients with heart failure with reduced ejection fraction: a network meta-analysis. Sleep Breath 26, 1227–1235 (2022). https://doi.org/10.1007/s11325-021-02512-y

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  • DOI: https://doi.org/10.1007/s11325-021-02512-y

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