Cardiovascular Burden of Narcolepsy Disease (CV-BOND): a real-world evidence study

Abstract

Study objectives: Narcolepsy is associated with cardiovascular risk factors; however, the risk of new-onset cardiovascular events in this population is unknown. This real-world study evaluated the excess risk of new-onset cardiovascular events in U.S. adults with narcolepsy.

Methods: A retrospective cohort study using IBM MarketScan administrative claims data (2014-2019) was conducted. A narcolepsy cohort, comprising adults (≥18 years) with at least two outpatient claims containing a narcolepsy diagnosis, of which at least one was non-diagnostic, was matched to a non-narcolepsy control cohort (1:3) based on cohort entry date, age, sex, geographic region, and insurance type. The relative risk of new-onset cardiovascular events was estimated using a multivariable Cox proportional hazards model to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: The narcolepsy and matched non-narcolepsy control cohorts included 12 816 and 38 441 individuals, respectively. At baseline, cohort demographics were generally similar; however, patients with narcolepsy had more comorbidities. In adjusted analyses, the risk of new-onset cardiovascular events was higher in the narcolepsy cohort compared with the control cohort: any stroke (HR [95% CI], 1.71 [1.24, 2.34]); heart failure (1.35 [1.03, 1.76]); ischemic stroke (1.67 [1.19, 2.34]); major adverse cardiac event (1.45 [1.20, 1.74]); grouped instances of stroke, atrial fibrillation, or edema (1.48 [1.25, 1.74]); and cardiovascular disease (1.30 [1.08, 1.56]).

Conclusion: Individuals with narcolepsy are at increased risk of new-onset cardiovascular events compared with individuals without narcolepsy. Physicians should consider cardiovascular risk in patients with narcolepsy when weighing treatment options.

Keywords: cardiovascular; comorbidities; narcolepsy; stroke.

Graphical Abstract

Figure 1.

Study design. ^aInclusion criteria included ≥6 months of continuous enrollment. ^bPatients were censored at discontinuation of insurance coverage, at the end of the study period (for those continuously enrolled), or at first qualifying diagnosis for the outcome of interest.

Figure 2.

Unadjusted incidence rates for new-onset cardiovascular events in patients with narcolepsy and matched non-narcolepsy controls. AFib, atrial fibrillation; CVD, cardiovascular disease; MACE, major adverse cardiac event; MI, myocardial infarction; ns, p ≥ .05.

Figure 3.

Adjusted HRs (95% CI) for incidence of new-onset cardiovascular events in patients with narcolepsy and matched non-narcolepsy controls. The relative risk of new-onset cardiovascular events between the narcolepsy and non-narcolepsy cohorts was estimated using a multivariable Cox proportional hazards model adjusted for age, sex, region, insurance type, and relevant comorbidities (Supplementary Table S3 lists the comorbidities adjusted for in the analysis). Adjusted HRs and 95% CIs are reported here. There were insufficient events to derive an HR for myocardial infarction. CI, confidence interval; CVD, cardiovascular disease; HR, hazard ratio; MACE, major adverse cardiac event.

Figure 4.

Sensitivity analysis: adjusted HRs (95% CI) for incidence of new-onset cardiovascular events in patients with (A) narcolepsy subtype 1 versus matched controls and (B) narcolepsy subtype 2 versus matched controls. CI, confidence interval; CVD, cardiovascular disease; HR, hazard ratio; MACE, major adverse cardiac event.

Figure 4.

Sensitivity analysis: adjusted HRs (95% CI) for incidence of new-onset cardiovascular events in patients with (A) narcolepsy subtype 1 versus matched controls and (B) narcolepsy subtype 2 versus matched controls. CI, confidence interval; CVD, cardiovascular disease; HR, hazard ratio; MACE, major adverse cardiac event.