Weighing Cardiovascular Risk When Treating Narcolepsy

Rami H. Ben-Joseph, PhD

At the 2022 American Academy of Neurology (AAN) Annual Meeting, April 2-7, in Seattle, Washington, Jazz Pharmaceuticals presented data on a new analysis that estimates the risk of cardiovascular and renal comorbidities in adults with narcolepsy. Using administrative claims databases, investigators matched patients without narcolepsy (n = 38,441) 3:1 to patients with narcolepsy (n = 12,816) by calendar date of cohort entry, age, gender, US geographic region, and insurance type.

Compared with matched controls without narcolepsy, those with narcolepsy had increased risk in several outcomes, demonstrated by adjusted HRs derived from incidence rates. These included any stroke (HR, 1.71; 95% CI, 1.24-2.34), edema (HR, 1.61; 95% CI, 1.28-2.03), heart failure (HR, 1.35; 95% CI, 1.03-1.76), ischemic stroke (HR, 1.67; 95% CI, 1.19-2.34), major adverse cardiac event (HR, 1.45; 95% CI, 1.20-1.74), and any cardiovascular disease excluding hypertension (HR, 1.30; 95% CI, 1.08-1.56). Additionally, investigators also showed increased risk in grouped instances of stroke, atrial fibrillation, or edema (HR, 1.48; 95% CI, 1.25-1.74).¹

NeurologyLive^® reached out to lead investigator Rami H. Ben-Joseph, PhD, executive director, Global Big Data Real-World Evidence, Jazz Pharmaceuticals, to learn more about the findings and how they can be interpreted. He provided insight on the research needed to expand these data, how the diagnostic process for narcolepsy may change, and whether cardiovascular measures are something clinicians should more closely monitor in these patients.

NeurologyLive®: For our audience, can you discuss how you went about conducting this study?

Rami H. Ben-Joseph, PhD: We conducted a retrospective analysis of US Healthcare claims from the IBM MarketScan database from January 1, 2014, to June 30, 2019. Eligible patients were at or above 18 years of age and had continuous medical and prescription coverage on cohort entry. Cardiovascular outcomes assessed included any stroke, atrial fibrillation, heart failure, myocardial infarction, among others. Each analysis was applied to a patient population that did not have an event of interest in the 6-month period prior to study entry. Patients were followed from 1 day after cohort entry until they experienced the outcome of interest for that analysis, or end of study period. Differences in outcome incidences between the narcolepsy and nonnarcolepsy cohorts were evaluated using a Cox proportional hazard model adjusted for age, sex, region, insurance type and relevant morbidities and comorbidities.

How do these data impact the screening and diagnostic process for those with narcolepsy?

Prior research has shown that high rates of comorbidities occur in patients with narcolepsy. The CV-BOND study suggests that the clinical profile of patients with narcolepsy is dynamic, evolving over time, placing a progressively greater burden on patients and accelerating their risk of poor cardiovascular outcomes in the future. The study also demonstrated that patients who do not present early on with cardiovascular disease will accumulate cardiovascular risk at a greater rate over time due to the biological consequences associated with narcolepsy. These results confirm that physicians should consider current and future cardiovascular risk when considering treatment options for patients with narcolepsy.

Should cardiovascular measures be something that neurologists should consistently be checking with their patients?

Conversations about cardiovascular health are often held between a patient and a primary care physician and these discussions should occur regularly with neurologists as well. The relationship between sleep disorders, and sleep-related disorders, such as sleep apnea, and poor cardiovascular functioning is well-established. We observed a similar directionality and magnitude of risk when measuring incident cardiovascular events with narcolepsy as has been reported for obstructive sleep apnea patients, many of whom also have comorbid sleep disorders. As some chronic cardiovascular conditions are asymptomatic, rigorous educational programs to improve disease surveillance in vulnerable populations could optimize patient care.

What remains the greatest challenges for patients with narcolepsy? Is it drug development or consistency in conducting quality studies?

The narcolepsy community lives with complex and severe conditions, and we’ve been working for many years to grow our understanding of the best way to manage this disorder. More needs to be done to help people experiencing symptoms identify the condition and seek a diagnosis, and progress can be made to ensure healthcare providers are considering a patients’ holistic health. Total risk value, including the risk of future CV events, must be considered.

What other types of cardiovascular-related narcolepsy research needs to be conducted? What else do we not know about yet?

I am encouraged by the continued examination of data, specifically real-world evidence, because it provides insights within the context of a patients’ daily life. Real-world data in narcolepsy has allowed us to understand patient outcomes more broadly, and whether patients are at a high or low risk for a cardiovascular event or another comorbidity. At Jazz, our goal is to think more holistically about patients’ health so they can live fuller lives and we are proud of our focus on identifying and developing therapies for people with serious sleep disorders.

Which areas of AAN are you most excited for? Are there trends in the sleep disorders space that make you excited as well?

Jazz presented insightful research on the debilitating burden of idiopathic hypersomnia as well as safety, efficacy, and quality of life data of our lower sodium oxybate therapy for the treatment of patients with narcolepsy and idiopathic hypersomnia. As long-time leaders in sleep medicine, we’re proud to be making strides in sleep research and expanding our knowledge of these complex and severe sleep disorders. We look forward to progressing our efforts to provide novel, life-changing medicines for people living with serious neurologic conditions and are hopeful that similar strides will continue to be made across the sleep disorder space to benefit patients.

Transcript edited for clarity. Click here for more coverage of AAN 2022.

REFERENCE
1. Ben-Joseph RH, Saad R, Black J, et al. Cardiovascular burden of narcolepsy disease (CV-BOND): a real-world evidence study. Presented at: 2022 AAN Annual Meeting; April 2-7; Seattle, Washington. Poster 1203.