Sacubitril-valsartan initiation in chronic heart failure patients impacts sleep apnea: the ENTRESTO-SAS study

Optimizing medical cardiac treatment for sleep apnoea (SA) in patients with chronic heart failure and reduced ejection fraction (HFrEF) is an expert Grade C recommendation based on six studies encompassing a total of 67 patients only. Whether sacubitril-valsartan (SV), a cornerstone of HFrEF medical treatment, impacts SA is unknown and requires evaluation.

The ENTRESTO-SAS trial is a six-centre, prospective, open-label real-life cohort study (NCT02916160). Ambulatory patients eligible for SV (i.e. HFrEF adults who remain symptomatic despite optimal treatment) were evaluated before and after 3 months of SV (including nocturnal ventilatory polygraphy); 118 patients were final analysed [median age was 66 (IQ_25-75 : 56-73) years, 81.4% male, 36.5% New York Heart Association III-IV, N-terminal pro-B-type natriuretic peptide level of 1564 (701-3376) ng/L, left ventricular ejection fraction of 30 (25-34)%, 60.7% ischaemic HFrEF, 97.5% initially treated with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, 83.9% with beta-blockers, 64.4% with mineralocorticoid receptor antagonists, and 74.6% with diuretics]. Three groups were defined according to initial central/obstructive apnoea-hypopnoea indices (AHIs): G1 (n = 49, AHI_central  ≥ 5/h and AHI_obstructive  < 15/h); G2 (n = 27, AHI_obstructive  ≥ 15/h); and G3 (n = 42, AHI_central  < 5/h and AHI_obstructive  < 15/h). At 3 months, the AHI (main predefined outcome) decreased significantly by -7.10/h (IQ_25-75 : -16.10 to 0.40; P < 0.001) in G1 + G2 without positive airway pressure treatment (45 patients, median initial AHI of 24.20 (IQ_25-75 : 16.40-43.50)/h). Of these, 24.4% presented an AHI decrease ≥50% and 37.78% had a final AHI < 15/h (tendency for improvement from an initial value of 20%: P = 0.0574). For G1 patients (n = 37), AHI significantly decreased from a median of 22.90 (16.00-43.50)/h to 19.20 (12.70-31.10)/h (P = 0.002). For G2 patients (n = 8), AHI decreased from a median of 30.10 (26.40-47.60)/h to 22.75 (14.60-36.90)/h (statistically non-significant, P = 0.059).

In this real-life population, SV treatment for 3 months in SA patients is associated with a significant decrease in AHI. These results support the current guidelines that recommend first an optimization of the HFrEF treatment in patients with HFrEF and central SA. A potential positive airway pressure sparing effect merits further investigation.