Approaches to management of rhabdomyolysis as the adverse effect of drug interaction between atorvastatin and sacubitril/valsartan: a case report

Abstract

Background Atorvastatin and sacubitril/valsartan (EntrestoTM) have been cornerstones in managing patients with coronary artery disease and heart failure. We report a case of life-threatening rhabdomyolysis associated with the co-administration of atorvastatin and sacubitril/valsartan. Case Summary A 58-year-old male with coronary heart disease and chronic heart failure treated with the optimal dose of atorvastatin and other cardiovascular medications was frequently admitted for acute decompensation of heart failure. We decided to optimise his condition by adding sacubitril/valsartan to his treatment regime. He presented to our outpatient clinic with worsening myalgia and oliguria six days later. He was readmitted with markedly elevated serum creatinine kinase (94,850 U/L; normal range 32–294 U/L), deranged liver function tests and acute kidney injury. We withheld atorvastatin and sacubitril/valsartan and treated him with renal replacement therapy. Discussion Sacubitril inhibits the excretion of statins, thereby elevating serum statin concentration and increasing the likelihood of developing muscle-related toxicity. Co-administration of atorvastatin and sacubitril/valsartan should be monitored closely with laboratory investigations of creatinine kinase and liver and renal function. The physician may consider starting low-dose atorvastatin at 20 mg daily in combination with sacubitril/valsartan 24 mg/26 mg twice daily and titrating accordingly to optimal doses. Rosuvastatin could be an alternative to atorvastatin, as it has less drug–drug interaction with sacubitril, thereby reducing the adverse effect.

Detection of muscular system adverse reaction signals in sacubitril/valsartan treatment combined with statins

“…This may be related to the smaller impact of inhibition of OATP1B1 and OATP1B3 on the AUC of rosuvastatin ( Elsby et al, 2012 ). In the existing literature are five case reports of rhabdomyolysis caused by the combined use of sacubitril/valsartan and statins, four of which were associated with atorvastatin ( Faber et al, 2016 ; Chan KH et al, 2020 ; Siew et al, 2022 ; Zhao FK et al, 2022 ) and one with rosuvastatin ( Previsdomini et al, 2019 ). However, the present study did not detect a statistically significant association signal with rhabdomyolysis, consistent with findings from studies like ( Sunaga and Ryo 2021 ; Tomiko and Yonezawa, 2021 ).…”