Evaluation of rosuvastatin-induced QT prolongation risk using real-world data, in vitro cardiomyocyte studies, and mortality assessment

• Published in: Scientific reports Vol. 13; no. 1; p. 8108
• Main Authors: Koo, Yeryung, Hyun, Sung-Ae, Choi, Byung Jin, Kim, Yujeong, Kim, Tae Young, Lim, Hong-Seok, Seo, Joung-Wook, Yoon, Dukyong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.05.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/154/436/108; 692/4019/592; Action potential; Action Potentials - physiology; Atorvastatin; Calcium channels; Cardiomyocytes; Health risks; HERG protein; Humanities and Social Sciences; Humans; Induced Pluripotent Stem Cells; Laboratories; Long QT Syndrome - chemically induced; Mortality; Mortality risk; multidisciplinary; Myocytes, Cardiac; Pluripotency; Potassium channels (voltage-gated); Retrospective Studies; Risk assessment; Rosuvastatin Calcium - adverse effects; Science; Science (multidisciplinary); Stem cells
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-35146-z

Drug-induced QT prolongation is attributed to several mechanisms, including hERG channel blockage. However, the risks, mechanisms, and the effects of rosuvastatin-induced QT prolongation remain unclear. Therefore, this study assessed the risk of rosuvastatin-induced QT prolongation using (1) real-world data with two different settings, namely case–control and retrospective cohort study designs; (2) laboratory experiments using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM); (3) nationwide claim data for mortality risk evaluation. Real-world data showed an association between QT prolongation and the use of rosuvastatin (OR [95% CI], 1.30 [1.21–1.39]) but not for atorvastatin (OR [95% CI], 0.98 [0.89–1.07]). Rosuvastatin also affected the sodium and calcium channel activities of cardiomyocytes in vitro. However, rosuvastatin exposure was not associated with a high risk of all-cause mortality (HR [95% CI], 0.95 [0.89–1.01]). Overall, these results suggest that rosuvastatin use increased the risk of QT prolongation in real-world settings, significantly affecting the action potential of hiPSC-CMs in laboratory settings. Long-term rosuvastatin treatment was not associated with mortality. In conclusion, while our study links rosuvastatin use to potential QT prolongation and possible influence on the action potential of hiPSC-CMs, long-term use does not show increased mortality, necessitating further research for conclusive real-world applications.