Narcolepsy and risk of cardiovascular outcomes beyond stimulant use

We aimed to assess associations between narcolepsy and cardiovascular disease risk while accounting for stimulant use in clinical practice.

Using 2005-2021 MarketScan Commercial and Medicare Supplemental databases, we identified patients with newly diagnosed narcolepsy using International Classification of Diseases, Ninth or Tenth, Clinical Modification diagnosis codes, were matched at a ratio of 1:3 patients without narcolepsy or hypersomnia using propensity score matching based on baseline demographics, comorbidities, and medication use. Primary outcomes included time to first (1) composite cardiovascular disease event and (2) major adverse cardiac event. Multivariable Cox proportional hazards regression models were used to compare outcome risks between groups, following PS matching, adjusting for time-fixed and time-varying variables, including stimulant use. Individual outcomes were examined separately and analyses were stratified by age, sex, and selected comorbidities.

After PS matching, data from 134967 patients (mean [SD] age, 39.9 [16.8] years; 61.5% female) were included in final analyses. Following adjustment of baseline and time-varying covariates, patients with narcolepsy had increased risks of cardiovascular disease (adjusted hazard ratio, 1.89 [95% CI = 1.71 to 2.09]) and major adverse cardiac event (adjusted hazard ratio,1.95 [95% CI = 1.70 to 2.23]) compared with patients without narcolepsy. Results remained consistent across individual cardiovascular diseases and major adverse cardiac events. Subgroup analyses yielded similar findings.

After adjusting for stimulant use, this cohort study found that patients with narcolepsy experienced increased risk of developing cardiovascular disease compared with patients without narcolepsy. This finding suggests that patients with narcolepsy may benefit from routine screening and monitoring for cardiovascular events. Statement of Significance This study enhances our understanding of the association between narcolepsy and cardiovascular events by employing a robust causal inference framework and adjusting for medications used to manage narcolepsy symptoms, which are known to be associated with cardiovascular risk. The large population-based cohort study included 34 562 patients with narcolepsy and 100 405 propensity score-matched patients without narcolepsy. Patients with narcolepsy had an increased risk of developing cardiovascular events compared to without narcolepsy controls, even after adjusting for medication use, including stimulants. These findings highlight the importance of routine cardiovascular screening and monitoring for patients with narcolepsy to mitigate potential risks.