Impact of sacubitril valsartan on sleep apnea in heart failure patients with reduced ejection fraction (SV-SLEEP): a systematic review and meta-analysis

Sleep apnea (SA) is identified among the most common comorbidities in heart failure patients with reduced ejection fraction (HFrEF) and potentially impacts prognosis of heart failure. Sacubitril-valsartan (SV) can attenuate SA development via several pathophysiologic mechanisms.

To evaluate the effects of initiating SV therapy on cardiorespiratory parameters in patients with HFrEF and SA.

A systematic review was conducted according to Cochrane Handbook and the PRISMA statement. A comprehensive systematic literature search was performed using EMBASE and MEDLINE, and Cochrane Library. RStudio software was used to pool baseline characteristics and calculate pooled mean difference (MD) with 95% confidence intervals (CI). Random-effects model was used to allow a more conservative assessment of the pooled effect size.

Six studies enrolling 409 patients were included. The pooled mean age was 65.18 (95% CI: 63.46; 66.90) years. Males accounted for 80.0% (95% CI: 75.0; 84.0) and smokers for 22.0% (95% CI: 17.0; 28.0) of patients. Most patients were taking beta-blockers (93.0%, 95% CI: 79.0; 98.0), and loop diuretics (81.0%, 95% CI: 52.0; 94.0). Up to half of the patients have implantable cardiac devices (Table 1). After 3 – 6 months of SV administration, there was significant improvement in natriuretic peptide levels (-784.62 pg/mL, 95% CI: -969.91; -599.32, P< 0.0001) and echocardiographic parameters such as LVEF (4.43%, 95% CI: 1.17; 7.69, P=0.0077), LVEDD (-3.39 mm, 95% CI: -4.4969; -2.2784, P<0.0001), TAPSE (1.18 mm, 95% CI: 0.49; 1.87, P=0.0008), LAVI (-6.03 mL/m2, 95% CI: -12.31; -0.76, p=0.0266), and sPAP (-3.73 mmHg, 95% CI: -5.84; -1.62, p=0.0005) compared to baseline values. Moreover, SV caused significant reduction in AHI (-5.35 events/h, 95% CI: -6.60; -4.10, p<0.0001) and TC90% (-6.53%, 95% CI: -8.44; -4.63, p<0.0001) values, as well as significant increase in oxygen saturation (0.58%, 95% CI: 0.28; 0.88, p=0.0002) (Table 2).

Sacubitril-valsartan significantly improved the cardiorespiratory parameters in patients with HFrEF and SA.