Effect of suvorexant on nighttime blood pressure in hypertensive patients with insomnia: The SUPER‐1 study

Abstract

Orexins are neuropeptides that play a role in maintaining wakefulness and contribute to central regulation of cardiovascular function. This first multicenter, randomized, double‐blind study investigated the effects of suvorexant, a reversible dual orexin receptor antagonist, on nighttime blood pressure (BP) in patients with insomnia and hypertension. After a 4‐week run‐in period, adult outpatients (n = 82) with treated hypertension (clinic SBP <160 mm Hg) and insomnia were treated with suvorexant 20 mg/d or placebo before bedtime for 2 weeks. Twenty‐four‐hour ambulatory BP monitoring was performed at baseline and the end of treatment, and home BP measurements (morning and evening) were taken daily. Nighttime systolic BP (SBP), the primary endpoint, decreased slightly from baseline to week 2 in both the suvorexant and placebo groups (−4.4 vs −1.8 mm Hg; P = 0.494). Clinic, 24‐hour, daytime and morning SBP (ambulatory blood pressure monitoring) also decreased slightly and similarly from baseline in both groups. In this study, suvorexant had no overall effect on BP in patients with insomnia and treated hypertension.

Type 5 phosphodiesterase (PDE5) and the vascular tree: From embryogenesis to aging and disease

“…The reduction of pulmonary vascular resistance and pressure after selective PDE5 inhibition are also associated with blood decrease of Endothelin-1 (ET-1) and attenuation of lung vessel hypoxia-induced inflammatory cytokine expression (Rossi et al, 2008) (Tsai et al, 2006). Recent clinical trials have succeeded in demonstrating the efficacy of sildenafil alone or in combination with ET-1 receptor antagonists to improve physical performances of patients affected by pulmonary hypertension alone or complicated by collagenopathies (SUPER-1 and COMPASS-2, respectively (Kario et al, 2019;Krishnan and Horn, 2016)). Covid-19 viral lung infection, the pandemia that is currently causing thousands of victims for respiratory insufficiency, has been hypothesized to affect not only the alveolar compartment but also the pulmonary microvasculature.…”

Insomnia and hypertension: A misty landscape

“…In the current issue of the Journal, Kario and colleagues conducted the SUPER‐1 study to investigate whether the DORA suvorexant exhibited BP‐lowering effects in patients with insomnia and hypertension . After a 4‐week ruin‐in period, 82 Japanese were randomized to receive an age‐adjusted dose of suvorexant (15 mg/d for individuals ≥ 65‐years or 20 mg/d for younger) (n = 40) or placebo (n = 42), for 2‐weeks.…”

“…The study by Kario et al is a clinically relevant study addressing the impact of DORA on reducing nighttime BP through a potential reduction in sympathetic tone and the potential suppression of the hypothalamic‐pituitary‐adrenal axis. However, suvorexant failed to establish any significant BP‐lowering effect in this short‐term period of 2‐weeks.…”

“…This is especially true, considering the significantly higher cardiovascular risk in patients with masked hypertension. 22 Kario et al 21 conducted a well-designed, double-blind, randomized study with significant strengths such as the well-balanced groups, the appropriate diagnosis of insomnia, and more importantly the adequate design with a ruin-in period, and appropriate BP measurements. We hope that this study will influence the field in order to include similar BP measurement protocols for future clinical trials, since for the time being the methodology of BP measurement seems to be the "Achilles…”

“…After 28 days of follow-up, estazolam was associated with a significantly greater reduction in office BP compared with placebo (−10.5/−8.1 vs − 3.4/−2.7 mm Hg, respectively; P < 0.001). Moreover, estazolam compared with placebo showed more likely to achieve well-controlled BP levels (74.8% vs 50.5%, respectively; P < 0.001), along with substantial improvements in several validated scales of sleep quality, anxiety, and depression.In the current issue of the Journal, Kario and colleagues conducted the SUPER-1 study to investigate whether the DORA suvorexant exhibited BP-lowering effects in patients with insomnia and hypertension 21. After a 4-week ruin-in period, 82 Japanese were randomized to receive an age-adjusted dose of suvorexant (15 mg/d for individuals ≥ 65-years or 20 mg/d for younger) (n = 40) or placebo (n = 42), for 2-weeks.…”