Falls, injuries from falls, and a lower QOL are linked to nocturia. Despite its frequency, nocturia is still not well controlled, undertreated, and underreported. Although the etiology of nocturia is complex, certain pathophysiological pathways have been identified, such as reduced bladder capacity, global or nocturnal polyuria (NP), and sleep disturbances. Nocturia's etiology is typically not isolated, and patients often appear with a variety of medical comorbidities that make diagnosis and treatment more difficult.
Epidemiological research revealed a strong correlation between nocturia and hypertension. Anti-hypertensive medications (AHTs) have also been linked in several studies to nocturia and other lower urinary tract symptoms. Nevertheless, it is unclear how new AHTs affect nocturia. 
A first-in-class angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan (Sac/Val) simultaneously inhibits neutral endopeptidase and blocks angiotensin II receptor-1. It is currently approved for use as an antihypertensive medication and for the treatment of chronic heart failure. Most significantly, neprilysin inhibits the sympathetic nervous system, the renin-angiotensin-aldosterone system, and vasodilatory, diuretic, natriuretic, and aldosterone secretion via binding to natriuretic peptide receptors (ref 1). Because of its distinct diuretic and natriuretic effects, it may be used to treat resistant hypertension. This study aimed to confirm whether Sac/Val, which has an improving effect on refractory hypertension, can improve nocturia.

The primary outcome was the improvements of nocturia in a cohort of hypertension patients. For this purpose, we compared their night-time urinary frequency before and after the use of Sac/Val.
The primary outcome was a change in average voiding frequency at night measured using a voiding diary. The following items were used as secondary outcomes. Pittsburgh Sleep Quality Index–Japanese Version（PSQI–J） , Nocturia Quality of Life Questionnaire（N–QOL）, Overactive Bladder Symptom Score（OABSS）, International Prostate Symptom Score (IPSS), and QOL.

Eighteen hypertension participants with nocturia were enrolled. The mean age of the patients was 66.7 years. The mean nighttime frequency and NPi at baseline were 3.31±1.45 voids and 48.1±13.0%, respectively. The nighttime frequency was significantly decreased (2.10±1.03:  Table 1a), The NPi were 39.7±11.4% in 12 weeks, decreased significantly compared to baseline. The PSQI–J total score was significantly lower at 12 weeks after treatment. There were no items with significant differences compared to the baseline. In the total N–QOL score was significantly lower at 12 weeks after treatment (Table 1b).  None of the evaluated IPSS parameter and QOL, were not significantly different. The nocturia score in OABSS was significantly lower in 12 weeks after treatment (Table 1c).

This study is the first to report that Sac/Val improves nocturia. NP has been associated with a variety of medical conditions (ref 2). The effects of AHTs on NP are not entirely understood. Many studies have found that Sac/Val has a stronger antihypertensive impact than angiotensin II receptor blockers, which is most likely due to sacubitril's natriuretic/diuretic and direct vasodilatory properties, which enhance the biological activity of natriuretic peptides. The mechanism of action of Sac/Val may be beneficial for NP (figure 1). Patients who visit cardiology departments do not often complain of nocturia. In this study, nocturia and NPi improved with lowering blood pressure. This suggests that cardiovascular disease may be an often-overlooked factor in the cause of nocturia. Therefore, a multidisciplinary approach is essential for the management of NP, and there is a need to promote collaboration between specialties with an emphasis on developing more patient-specific treatments.

Sac/Val, which has an improving effect on refractory hypertension, may also improve nocturia. A multidisciplinary approach is essential in the management of nocturnal polyuria, and there is a need for increased interdisciplinary collaboration with an emphasis on developing treatments more specific to cardiovascular conditions.

Rev Port Cardiol. 2017;36:655-668
Neurourol Urodyn. 2020;39:1098–107