Background Restless legs syndrome (RLS) is associated with higher cardiovascular disease (CVD) risk. However, it remains unknown whether treatment of RLS lowers the cardiovascular risk associated with RLS. Methods and Results All data were collected retrospectively, but subjects were prospectively followed forward in time to determine outcomes of interest. We used the Truven Health MarketScan Commercial Claims and Encounters database from January 1, 2006, through December 31, 2014. Participants were 169 393 individuals, which included 24 199 nonpregnant participants with an RLS diagnosis (16 694 receiving treatments for RLS and 7505 without treatment) during 2006 to 2008 and 145 194 age- and sex-matched participants without RLS. All participants were free of CVD before January 1, 2009 (analysis baseline). Incident CVD cases (myocardial infarction, angina, stroke, atrial fibrillation, and heart failure) were identified. We adjusted for potential confounders, such as presence of chronic conditions and medication use. We identified 16 574 incident CVD cases during 2009 to 2014. Relative to the non-RLS group, the adjusted hazard ratio (HR) for future CVD was 1.26 (95% CI, 1.20-1.32) (P<0.001) for the RLS with treatment group, and 1.53 (95% CI, 1.42-1.65) (P<0.001) for the RLS without treatment group. Significant lower CVD risk was observed for all different RLS treatments, including dopaminergics, anticonvulsants, benzodiazepines, and opiates (adjusted HRs range, 0.71-0.84; P<0.001 for all), except for ergot-dopamine use. Conclusions RLS was associated with higher future CVD risk. However, RLS was associated with statistically significantly less future cardiovascular risk in RLS patients with treatment than in those without treatment.
Keywords: cardiovascular disease; cohort study; restless legs syndrome; stroke; treatment.