Cardiovascular risk in narcolepsy: Comparison of type 1 and type 2 in a real-world cohort

To compare the differences in the risk of cardiovascular disease (CVD) events between narcolepsy type 1 (NT1) and type 2 (NT2) among patients with narcolepsy, while accounting for real-world use of stimulants.

Using the 2005-2023 MarketScan Commercial and Medicare Supplemental databases, we identified patients newly diagnosed with narcolepsy, either NT1 or NT2, using International Classification of Diseases, Ninth or Tenth Revision, Clinical Modification diagnosis codes. Stabilized inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between the NT1 and NT2 groups. Primary outcomes included time to first (1) composite CVD event and (2) major adverse cardiovascular event (MACE). We used multivariable Cox proportional hazards regression models following IPTW to estimate adjusted hazard ratios (AHRs), accounting for time-fixed and time-varying covariates, including stimulant use. Individual cardiovascular outcomes were assessed separately, and analyses were stratified by age and sex.

After IPTW, the overall effective sample size was 30,154 patients (NT1 = 3,068, NT2 = 27,086; mean [SD] age, 39.8 [16.5] years; 61.8% female). In models adjusting for baseline covariates and time-varying stimulant use, there was no difference in risk of CVD (AHR, 0.95; 95% CI, 0.75-1.22) or MACE (AHR, 0.98; 95% CI, 0.72-1.33) between NT1 and NT2. Results were consistent across individual CVD and MACE outcomes, as well as in subgroup analyses by age and sex.

Findings from this IPTW cohort study suggest that, after adjusting for medication use, there was no significant difference in cardiovascular risk between individuals with NT1 and NT2. Patients with narcolepsy are at elevated cardiovascular risk, but little is known about how this risk differs between narcolepsy type 1 (NT1) and type 2 (NT2). Previous studies have not directly compared cardiovascular risk by narcolepsy subtype while accounting for real-world use of medications, including stimulants, which may change over time and influence outcomes. In this large, national cohort of commercially insured individuals, we found no significant difference in cardiovascular disease risk for individuals with NT1 vs. NT2 after adjusting for baseline characteristics and the use of narcolepsy medications, including stimulants. These findings address the gap in the literature regarding cardiovascular risks across narcolepsy subtypes and may inform clinical management of the disorder.