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Abstract Introduction Emerging research suggests that narcolepsy, a chronic disabling condition characterized by excessive daytime sleepiness, directly impacts the cardiovascular system, leading to increased risk of cardiovascular disease (CVD). Existing studies evaluating CVD risk among persons with narcolepsy (PWN) have not considered medications to treat the symptoms of narcolepsy (e.g., stimulants). We aimed to assess the real-world association of narcolepsy with CVD risk while accounting for medications. Methods We conducted a retrospective cohort study using 2005-2021 MarketScan® Commercial and Medicare Supplemental databases. Patients with newly diagnosed narcolepsy with ◻2 outpatient claims identified using International Classification of Diseases – Clinical Modification diagnosis codes were included (narcolepsy group). A comparison cohort of patients without narcolepsy and hypersomnia (non-narcolepsy group) was matched at a ratio of 1 up to 3 using propensity score (PS) matching based on baseline demographics, comorbidities, and medication use. After PS matching, we used multivariable Cox regression to compare the risks of CVD (i-e., stroke, atrial fibrillation, heart failure (HF), myocardial infarction (MI), or acute coronary syndrome) and major adverse cardiac events (MACE) (i-e., MI, ischemic stroke, HF, acute coronary syndrome, coronary artery bypass grafting, or percutaneous coronary intervention) between the two groups after controlling for baseline wake promoting agents and stimulants use, and post-index time-varying stimulants use. Follow-up continued until the occurrence of outcomes, end of enrollment, or December 31, 2021. Results 134,967 patients (34,562 PWN and 100,405 non-narcolepsy; mean age 40±16.78 years and 62% female) were identified. The crude incidence of CVD was 1.50 and 0.85 per 100 person-years for narcolepsy and non-narcolepsy groups, respectively. After controlling for baseline and time-varying covariates, PWN was associated with a 93% higher CVD risk compared to non-narcolepsy group (adjusted hazard ratio (aHR), 1.93; 95% confidence interval (95% CI), 1.75-2.13). Similarly, PWN was associated with a 97% higher MACE risk compared to non-narcolepsy group (aHR,1.97; 95%CI, 1.72-2.26). Conclusion In this PS-matched cohort study, PWN experienced increased risk of developing CVD or MACE relative to propensity-matched patients without narcolepsy after controlling for baseline medication use (stimulant and wake promoting agent), and post-index time-varying stimulant use. Support (if any) Sleep Research Society Foundation (23-FRA-001).
Riaz et al. (Sat,) studied this question.