What is the evidence for benefit of treatment options for central sleep apnea (CSA)?

Treatment Options for Central Sleep Apnea: Evidence and Recommendations

For patients with central sleep apnea (CSA), treatment should be tailored to the underlying etiology, with continuous positive airway pressure (CPAP) as first-line therapy for most forms of CSA, while adaptive servo-ventilation (ASV) should be avoided in patients with heart failure with reduced ejection fraction due to increased mortality risk. 1

Treatment Approaches Based on CSA Etiology

First-Line Therapies:

• CPAP therapy is suggested as initial treatment for most forms of CSA including primary CSA, CSA due to heart failure, medication/substance-induced CSA, treatment-emergent CSA, and CSA due to medical conditions 1
• CPAP has been shown to reduce apnea-hypopnea index (AHI) to fewer than 15 events/hour in approximately 45% of patients with CSA associated with heart failure 2
• In a longitudinal cross-sectional study, 42.2% of CSA patients showed positive response to CPAP therapy, particularly those with congestive heart failure and ischemic heart disease 3

Second-Line Therapies:

• Bilevel positive airway pressure (BiPAP) with backup rate is suggested when CPAP is ineffective for primary CSA, medication/substance-induced CSA, treatment-emergent CSA, and CSA due to medical conditions 1
• BiPAP without backup rate is not recommended for CSA treatment 1
• In patients unresponsive to CPAP alone, 28.1% responded to BiPAP therapy, particularly those with history of opioid use 3

Supplemental Oxygen:

• Low-flow oxygen therapy is suggested specifically for CSA due to heart failure and high-altitude CSA 1
• When combined with CPAP, supplemental oxygen provided benefit in 20.3% of CSA patients who did not respond to CPAP alone 3
• However, two studies have shown that supernormal amounts of oxygen may further impair cardiac function in heart failure patients 2

Pharmacological Therapy:

• Acetazolamide (a carbonic anhydrase inhibitor) is suggested for all forms of CSA including primary CSA, heart failure-related CSA, medication/substance-induced CSA, treatment-emergent CSA, and high-altitude CSA 1
• Acetazolamide has been shown to decrease central apneas during short-term use, though results have been variable with prolonged administration 4
• Other drug therapies have not demonstrated sufficient efficacy for CSA treatment 2

Special Considerations for Heart Failure Patients

Adaptive Servo-Ventilation (ASV):

• ASV should be avoided in patients with heart failure with reduced ejection fraction (HFrEF) due to increased cardiovascular mortality demonstrated in the SERVE-HF trial 2
• The SERVE-HF trial showed worsened all-cause and cardiovascular mortality with ASV in HFrEF patients despite reduction in AHI 2
• For other forms of CSA, ASV may be considered with careful patient-provider shared decision-making 1
• ASV treatment in HFrEF patients should be limited to specialized centers with close monitoring 1

Transvenous Phrenic Nerve Stimulation (TPNS):

• TPNS is suggested as an option for primary CSA and CSA due to heart failure 1
• However, TPNS is invasive, not universally accessible, associated with high costs, and carries risk of serious adverse effects in approximately 10% of patients 2, 1
• Other treatment options should typically be considered before TPNS 1

Treatment Algorithm for CSA

1. Optimize therapy for underlying conditions contributing to CSA (heart failure, opioid use, etc.) 1
2. First-line therapy: Trial of CPAP for most forms of CSA 1
3. If inadequate response to CPAP:
   • For heart failure patients: Consider low-flow oxygen or CPAP + oxygen 3, 1
   • For non-heart failure patients: Consider BiPAP with backup rate 1
4. If still inadequate response:
   • Consider acetazolamide 1, 4
   • Consider ASV (except in patients with HFrEF) 1
   • Consider TPNS in specialized centers for refractory cases 1

Monitoring and Follow-up

• Persistence of central respiratory events should prompt re-evaluation of underlying risk factors 1
• Approximately 9.4% of patients (particularly older patients with CHF and IHD) may be non-responsive to all conventional approaches 3
• Focus on improving patient-reported outcomes rather than solely eliminating disordered breathing events 1

Pitfalls and Caveats

• ASV is contraindicated in patients with HFrEF due to increased mortality risk 2
• Benzodiazepines should not be prescribed for long-term treatment of CSA associated with heart failure 2
• Treatment decisions should prioritize improvement in symptoms and quality of life rather than normalization of AHI alone 1
• The evidence base for CSA treatment is generally of low to very low certainty, requiring careful individualized decision-making 1