Riluzole is Associated With Reduced Risk of Heart Failure

Background: Reduction of intracellular Na+ accumulation through late Na+ current inhibition has been recognized as a target for cardiac Ca2+ handling which underlies myocardial contractility and relaxation in heart failure (HF). Riluzole, a Na+ channel blocker with enhancement of Ca2+ activated K+ channel function, used for management of amyotrophic lateral sclerosis (ALS), is effective in suppressing Ca2+ leak and therefore may improve cardiac function. Objectives: The study aim was to investigate whether riluzole lowers HF incidence. Methods: Rates of HF incident were compared using a commercial insurance and Medicare supplement claims databases. Patients with a filled riluzole prescription (treatment) between 06/2009 and 12/2019 were compared to those with no riluzole (control). We excluded HF patients during the 180 day baseline period. Study endpoint was the first HF diagnosis from the index riluzole prescription or ALS diagnosis. HF onset was compared between the propensity score matched treatment and control cohorts. Results: The matched cohort consisted of 4,060 pairs of riluzole/control patients. The 24 month cumulative incidence of HF onset for riluzole vs. control patients was 4.96% vs. 7.27%, calculating hazard ratio (HR) [95% CI, p value] of 0.55 [0.40 to 0.76, p<0.01]. The HR estimates favoring riluzole over the ALS control were consistent across the 3 months to 2 year follow up. The clinically and statistically significant effect on HF onset was driven by the lower rate of HFrEF with the 2 year HR [95% CI] of 0.46 [0.21 to 0.99]. Conclusions: Riluzole is associated with a lower rate of HF onset, suggesting a potential prevention strategy for early management. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded in part by National Institutes of Health supported this work from grants R01HL155378 and R01NS121234 (to Radwański), R01HL142588 and R01HL166604 (to Terentyev). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was deemed exempt by the University of Illinois Institutional Review Board. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.