Ohayon Study | 2013
Comorbidities in Narcolepsy Disease
An interview-based analysis that included 320 people with narcolepsy (≥18 years of age) and 1464 matched controls from the general population investigated certain cardiovascular conditions observed among people with a narcolepsy diagnosis compared with matched controls.*
Increased Risk in People With Narcolepsy vs Controls
The mean age of study participants was 40 years.
Adjusted odds ratios (95% CI).
1.5×
Hypercholesterolemia
(1.04-2.19)
P<0.5
P<0.5
2.1×
Heart disease
(1.22-3.51)
P<0.01
P<0.01
1.3×
Hypertension
(1.02-1.70)
P<0.05
P<0.05
*Controls without narcolepsy were matched 5:1 on age, sex, and body mass index.
Reference: Ohayon MM. Sleep Med. 2013;14(6):488-492.
Burden of Narcolepsy Disease Study | 2017 (Black)
A Higher Cardiovascular Comorbidity Burden for People With Narcolepsy
The Burden of Narcolepsy Disease (BOND) study was a retrospective medical claims data analysis that included a total of 9312 people with narcolepsy (≥18 years of age, continuously insured between 2006 and 2010) and 46,559 matched controls. In this study, people with narcolepsy had claims evidence suggesting significantly higher rates of comorbidities, including cardiovascular disease, vs matched controls.*
Increased Risk in People With Narcolepsy*
The mean age of BOND study participants was 46 years.
Adjusted odds ratios (95% CI).
Adjusted odds ratios (95% CI).
2.5×
Stroke
(2.3-2.7)
P<0.0001
P<0.0001
2.6×
Heart failure
(2.3-2.9)
P<0.0001
P<0.0001
1.6×
Cardiac arrest
(1.1-2.3)
P<0.0326
P<0.0326
1.6×
Myocardial infarction
(1.3-1.8)
P<0.0001
P<0.0001
In addition, hypertension occurred in a higher percentage of people with narcolepsy.
Benign hypertension: 36.8% in the narcolepsy group vs 26.5% in the control group
Hypertension NOS: 43.7% in the narcolepsy group vs 31.4% in the control group
NOS, not otherwise specified.
*Controls without narcolepsy were matched 5:1 for age, sex, region, and payer. The objective of the study was to evaluate medical comorbidity patterns in people with narcolepsy.
*Controls without narcolepsy were matched 5:1 for age, sex, region, and payer. The objective of the study was to evaluate medical comorbidity patterns in people with narcolepsy.
Reference: Black J. et al. Sleep Med. 2017;33:13-18.
Cohen Study | 2017
Greater Cardiometabolic Risks in People With Narcolepsy
This study was a community-based narcolepsy cohort confirmed by manual review of sleep history, polysomnogram, and multiple sleep latency test records compared with unaffected age- and sex-matched controls. Control subjects were chosen randomly from a pool of unaffected individuals at the time of the patient's narcolepsy diagnosis (ie, the index date for the case-control group) and matched 4:1 (n=272) with people with narcolepsy (n=68).
Cardiometabolic Comorbidities at Narcolepsy Diagnosis in People With Narcolepsy vs Matched Controls
Adjusted odds ratios (95% CI)
2.5×
Hyperlipidemia
(1.05-5.92)
P<0.5
P<0.5
2.7×
Hypertension
(1.22-5.93)
P<0.05
P<0.05
2.3×
Obesity
(1.13-4.56)
P<0.05
P<0.05
Reference: Cohen A et al. Sleep Med. 2018;43:14-18.
Cardiovascular Burden of Narcolepsy Study | 2023 (Ben-Joseph)
New-Onset Cardiovascular Events in Patients With Narcolepsy
The Cardiovascular Burden of Narcolepsy Disease (CV-BOND) study was a retrospective medical claims analysis designed to estimate the incidence of new-onset cardiovascular events in 12,816 adult patients with narcolepsy vs 38,441 matched controls without narcolepsy.*
CV-BOND: Increased Risk of
New-Onset Cardiovascular Events in Narcolepsy*
New-Onset Cardiovascular Events in Narcolepsy*
The mean age of the CV-BOND study participants was 38 years.
Adjusted hazard ratios (95% CI)
1.7×
Any stroke
(1.24, 2.34)
1.4×
Heart failure
(1.03, 1.76)
1.7×
Ischemic stroke
(1.19, 2.34)
1.5×
MACE
(1.20, 1.74)
1.3×
CV disease
(1.08, 1.56)
Evidence from CV-BOND suggests that the clinical profile of patients with narcolepsy evolves over time, with increased risk of cardiovascular outcomes with age.
MACE, major adverse cardiac event.
*The CV-BOND study was a retrospective medical claims analysis designed to estimate the incidence of new-onset cardiovascular comorbidities or events in adult patients with narcolepsy in the United States between January 1, 2014, and June 30, 2019. Eligible patients were 18 years of age and older with continuous medical and prescription coverage. Patients without narcolepsy were matched 3:1 to patients with narcolepsy by calendar date of cohort entry, age, sex, US geographic region, and insurance type. Excluded patients in each analysis with a history of that cardiovascular event in the 6 months prior to cohort entry. Patients remained eligible for inclusion in other cardiovascular event analyses; eg, a patient with a history of stroke could still be included in the HF and MACE analyses.
*The CV-BOND study was a retrospective medical claims analysis designed to estimate the incidence of new-onset cardiovascular comorbidities or events in adult patients with narcolepsy in the United States between January 1, 2014, and June 30, 2019. Eligible patients were 18 years of age and older with continuous medical and prescription coverage. Patients without narcolepsy were matched 3:1 to patients with narcolepsy by calendar date of cohort entry, age, sex, US geographic region, and insurance type. Excluded patients in each analysis with a history of that cardiovascular event in the 6 months prior to cohort entry. Patients remained eligible for inclusion in other cardiovascular event analyses; eg, a patient with a history of stroke could still be included in the HF and MACE analyses.
Reference: Ben-Joseph RH et al. Sleep. 2023;46(10):zsad161.
Kaufmann Study | 2024
Evidence for an Independent Association of Cardiovascular Disease in Patients With Narcolepsy
This retrospective cohort study used large representative commercial insurance claims databases to identify 34,562 newly diagnosed people with narcolepsy and a matched cohort of 100,405 people without narcolepsy or other hypersomnolence disorders to estimate risk outcomes for cardiovascular disease.*
Cardiovascular Events Post-Narcolepsy Diagnosis
The mean age of study participants was 40 years.
Hazard ratios (95% CI)
2.0×
Stroke
(1.82-2.29)
1.6×
Heart failure
(1.47-1.83)
1.8×
MACE
(1.66-1.99)
1.8×
CVD
(1.65-1.89)
1.6×
AFib
(1.40-1.77)
1.6×
MI
(1.37-1.96)
AFib, atrial fibrillation; CVD, cardiovascular disease; MACE, major adverse cardiac event; MI, myocardial infarction.
*Retrospective medical claims analysis including 34,562 people with narcolepsy (continuously insured between 2005 and 2021) and 100,405 matched controls. Controls were matched 3:1 on underlying demographics; the presence of relevant health conditions, including sleep apnea and diabetes; and other confounders. Evaluated post narcolepsy diagnosis for cardiovascular events as an independent risk factor for cardiovascular disease.
*Retrospective medical claims analysis including 34,562 people with narcolepsy (continuously insured between 2005 and 2021) and 100,405 matched controls. Controls were matched 3:1 on underlying demographics; the presence of relevant health conditions, including sleep apnea and diabetes; and other confounders. Evaluated post narcolepsy diagnosis for cardiovascular events as an independent risk factor for cardiovascular disease.
Important Safety Information
WARNING: CENTRAL NERVOUS SYSTEM DEPRESSION and ABUSE AND MISUSE.
- Central Nervous System Depression
XYWAV is a CNS depressant. Clinically significant respiratory depression and obtundation may occur in patients treated with XYWAV at recommended doses. Many patients who received XYWAV during clinical trials in narcolepsy were receiving CNS stimulants.
- Abuse and Misuse
The active moiety of XYWAV is oxybate or gamma-hydroxybutyrate (GHB). Abuse or misuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death.
Because of the risks of CNS depression and abuse and misuse, XYWAV is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the XYWAV and XYREM REMS.
Contraindications
XYWAV is contraindicated
- in combination with sedative hypnotics or alcohol and
- in patients with succinic semialdehyde dehydrogenase deficiency.
Warnings and Precautions
Central Nervous System Depression
The concurrent use of XYWAV with other CNS depressants, including but not limited to opioid analgesics, benzodiazepines, sedating antidepressants or antipsychotics, sedating anti-epileptic drugs, general anesthetics, muscle relaxants, and/or illicit CNS depressants, may increase the risk of respiratory depression, hypotension, profound sedation, syncope, and death. If use of these CNS depressants in combination with XYWAV is required, dose reduction or discontinuation of one or more CNS depressants (including XYWAV) should be considered.
After first initiating treatment and until certain that XYWAV does not affect them adversely (eg, impair judgment, thinking, or motor skills), caution patients against hazardous activities requiring complete mental alertness or motor coordination such as operating hazardous machinery, including automobiles or airplanes. Also caution patients against these hazardous activities for at least 6 hours after taking XYWAV. Patients should be queried about CNS depression-related events upon initiation of XYWAV therapy and periodically thereafter.
After first initiating treatment and until certain that XYWAV does not affect them adversely (eg, impair judgment, thinking, or motor skills), caution patients against hazardous activities requiring complete mental alertness or motor coordination such as operating hazardous machinery, including automobiles or airplanes. Also caution patients against these hazardous activities for at least 6 hours after taking XYWAV. Patients should be queried about CNS depression-related events upon initiation of XYWAV therapy and periodically thereafter.
Reference: Kaufmann CN, Riaz M, Park H, et al. Evidence for an independent association of cardiovascular disease in patients with narcolepsy. Poster presented at: Associated Professional Sleep Societies Annual Meeting (SLEEP 2024); June 1-5, 2024; Houston, TX.
Important Safety Information
WARNING: CENTRAL NERVOUS SYSTEM DEPRESSION and ABUSE AND MISUSE.
- Central Nervous System Depression
XYWAV is a CNS depressant. Clinically significant respiratory depression and obtundation may occur in patients treated with XYWAV at recommended doses. Many patients who received XYWAV during clinical trials in narcolepsy were receiving CNS stimulants.