Ajayi, Akinyemi

Introduction: Excess sodium intake is strongly linked with hypertension and cardiovascular disease (CVD); people with narcolepsy (PwN) have increased CV risk. Hypothesis: Switching from high-sodium oxybate (SXB; Xyrem ® ; 6–9 g for ≥6 wks) to low-sodium oxybate (LXB; Xywav ® ; same regimen) reduces mean 24-hr ambulatory systolic blood pressure (ASBP) after ≈6 wks in PwN, regardless of antihypertensive (anti-HTN) use and site type. Methods: XYLO, an open-label, single-arm study (NCT05869773), assessed PwN aged 18−70 y with office SBPs of 130−155 mmHg. The primary and key secondary endpoints were changes from baseline (BL) to end-of treatment (EOT) in mean 24-hr ASBP and seated resting (“office”) SBP (OSBP), respectively; exploratory endpoints were diastolic BP (DBP) changes. Changes are baseline adjusted. Prespecified subgroup analyses explored BL anti-HTN use and participation site (ie, site-based [at study site] vs decentralized [at-home]). Results: In 43 PwN (mean age, 45 y; female, 65%; anti-HTN, 33%), mean±SD BL OSBP and DBP were 138.0±5.7 and 85.2±6.6 mmHg, respectively. Mean±SD total SXB vs LXB dosages were 8.0±1.1 vs 8.1±1.1 g/night, reflecting 1457±206 vs 118±16 mg sodium (difference: ≈1339 mg); median 24-hr urinary sodium was 4232 mg/d at BL and 2703 mg/d at EOT (median change: 1288 mg/d). Mean change in 24-hr ASBP (least squares mean [95% CI]) was −4.1 (−6.9, −1.4; 1-sided P =0.0019) mmHg (Fig 1) ; mean change in OSBP was −9.2 (−11.9, −6.5; 1-sided P <0.0001). Mean changes in 24-hr ambulatory and office DBP were −2.3 (−4.1, −0.5; 2-sided P =0.0118; nominal) and −3.8 (−6.0, −1.6; 2-sided P =0.0014; nominal) mmHg, respectively. In subgroups, mean change in 24-hr ASBP was −4.6 (−9.6, 0.3) mmHg with BL anti-HTN use and −3.9 (−7.3, −0.5) mmHg without BL anti-HTN use; changes in OSBP were −11.8 (−16.5, −7.1) and −7.9 (−11.1, −4.6) mmHg. Mean change in 24-hr ASBP was −3.6 (−8.0, 0.9) mmHg for site-based and −4.5 (−8.1, −1.0) mmHg for decentralized participation. Corresponding changes in OSBP were −9.0 (−13.3, −4.6; site-based) and −9.3 (−12.8, −5.8; decentralized) mmHg with a downward trend over 6 wks ( Fig 2 ). Treatment-emergent adverse events (all mild/moderate) occurred in 40% of PwN (N=67). Conclusions: Switching from SXB to LXB reduced daily medication-related sodium intake in PwN and was associated with clinically meaningful BP reductions overall and across subgroups, consistent with evidence on dietary and medication-related sodium effects.

BACKGROUND: People with narcolepsy are at increased risk for hypertension and cardiovascular disease; excessive sodium intake is linked to both. METHODS: We studied patients with narcolepsy and office systolic blood pressures (BPs) of 130 to 155 mm Hg taking twice-nightly high-sodium oxybate for ≥6 weeks who switched to low-sodium oxybate at the same dosage. The primary end point was the change from baseline in mean 24-hour ambulatory systolic BP at the end of treatment (≈6 weeks after switching). Secondary and exploratory end points included changes in diastolic BP, office BP, and 24-hour sodium excretion. RESULTS: Patients (n=43) had a mean age of 45 years, were 65% female, 33% on antihypertensives, with baseline mean (SD) office BP of 138.0/85.2 (5.7/6.6). Mean (SD) total high- and low-sodium oxybate dosages of 8.0 (1.1) and 8.1 (1.1) g/night, respectively, represented 1456.5 (206.2) and 117.8 (16.3) mg of sodium. The median 24-hour urinary sodium was 4278 mg/d at baseline and 2703 mg/d at the end of treatment (median change, 1288 mg/d). Mean (SE) 24-hour ambulatory systolic BPs at baseline and study end were 132.3 (1.8) and 128.2 (1.8) mm Hg (least-squares mean change, −4.1 [95% CI, −6.9 to −1.4] mm Hg; 1-sided P =0.0019). BP changes by narcolepsy subtype, sex, body mass index, baseline office BP, and baseline antihypertensive use were consistent with the overall effect size. CONCLUSIONS: People with narcolepsy switching from high- to low-sodium oxybate showed substantially reduced daily medication-related sodium intake and significant 24-hour BP reductions. These results demonstrate the importance of reducing pharmaceutical sodium content in this elevated cardiovascular risk patient population. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05869773.