Annals of Medicine and Surgery · Oct 7, 2026
Phenotype-specific differences in mortality and cerebrovascular risk in narcolepsy type 1 and type 2: a real-world propensity score-matched cohort study
By Gautam N, Upadhyay A, Subedi BK et al.
Background: Narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2) are clinically distinct disorders, but comparative long-term data on hard outcomes remain limited. We compared all-cause mortality and major cerebrovascular and cardiovascular outcomes between NT1 and NT2 in a large real-world cohort. Materials and methods: This retrospective cohort study used the TriNetX US Collaborative Network, with analysis performed on 28 September 2025. Adults aged 18–75 years with NT1 (ICD-10-CM G47.411) or NT2 (ICD-10-CM G47.419) were identified. After 1:1 propensity score matching for demographics, comorbidities, lifestyle-related factors, and medication exposures, 19 907 matched pairs were analyzed. The primary outcome was all-cause mortality over 10 years. Secondary outcomes were ischemic stroke, major adverse cardiovascular events (MACE), arrhythmia, and sudden cardiac death. Hazard ratios (HRs) with 95% confidence intervals (CIs) were derived within the TriNetX analytics platform. Results: NT1 was associated with lower all-cause mortality than NT2 (1.57% vs 2.01%; HR 0.764, 95% CI: 0.659–0.885; P < 0.001). NT1 was also associated with a higher risk of ischemic stroke (1.49% vs 1.23%; HR 1.193, 95% CI: 1.006–1.415; P = 0.042). There were no statistically significant differences in MACE (HR 1.084, 95% CI: 0.941–1.249; P = 0.264), arrhythmia (HR 0.864, 95% CI: 0.740–1.009; P = 0.065), or sudden cardiac death (HR 0.844, 95% CI: 0.522–1.365; P = 0.489). Conclusion: In this matched real-world cohort, NT1 was associated with lower all-cause mortality but higher ischemic stroke risk compared with NT2. Because this was an observational analysis, these findings represent associations rather than causal effects and should be interpreted as hypothesis-generating; they support phenotype-aware risk assessment, especially the prospective validation of cerebrovascular risk in NT1.