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Riluzole, an Na<jats:sup>+<\/jats:sup> channel blocker with enhancement of Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup> channel function, used for management of amyotrophic lateral sclerosis (ALS), is effective in suppressing Ca<jats:sup>2+<\/jats:sup> leak and therefore may improve cardiac function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The study aim was to investigate whether riluzole lowers HF incidence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2010riluzole (control). We excluded HF patients during the 180\u2010day 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The matched cohort consisted of 4060 pairs of riluzole\/control patients. The 24\u2010month cumulative incidence of HF onset for riluzole versus control patients was 4.96% versus 7.27%, calculating hazard ratio (HR) [95% CI, <jats:italic>p<\/jats:italic>\u2010value] of 0.55 [0.40\u20130.76, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01]. The HR estimates favoring riluzole over the ALS control were consistent across the 3\u2009months to 2\u2010year follow\u2010up. The clinically and statistically significant effect on HF onset was driven by the lower rate of HFrEF with the 2\u2010year HR [95% CI] of 0.46 [0.21\u20130.99].<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Riluzole is associated with a lower rate of HF onset, suggesting a potential prevention strategy for early management.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.70033","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T13:41:07Z","timestamp":1736430067000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Riluzole is associated with reduced risk of heart failure"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8676-7434","authenticated-orcid":false,"given":"Kibum","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pharmacy Systems and Outcomes and Policy University of Illinois Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0124-0404","authenticated-orcid":false,"given":"Sodam","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Systems and Outcomes and Policy University of Illinois Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Katana","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Systems and Outcomes and Policy University of Illinois Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9530-7384","authenticated-orcid":false,"given":"Dmitry","family":"Terentyev","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology The Ohio State University  Columbus Ohio USA"},{"name":"The Frick Center for Heart Failure and Arrhythmia Dorothy M. 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