Potential Safety Signals for Rhabdomyolysis Associated With High-Potency Statin Use With or Without Sacubitril/Valsartan

Abstract

Regarding the drug interactions between sacubitril/valsartan and statins, we identified 3 reports of rhabdomyolysis with high-potency statins. However, it remains unknown whether the combined use of these medications could lead to additive or synergistic effects on rhabdomyolysis. This study aims to assess the disproportionality in reporting rhabdomyolysis for these medications when used alone or in combination. Case reports from the United States Food and Drug Administration's Adverse Event Reporting System from 1991 to Q4/2020 were used. Queries extracted reports based on exposure to statins alone, sacubitril/valsartan alone, and statin+sacubitril/valsartan each. Proportional reporting ratios (PRR) and 95% confidence intervals (CIs) were calculated, where a lower limit of the 95% CI (Lower 95% CI) value of ≥2.0 was interpreted as a safety signal. Lower 95% CIs for statins other than rosuvastatin alone demonstrated no potential safety signals for rhabdomyolysis, death, or the control event. The PRRs and 95% CI for rhabdomyolysis were 2.39 (2.01 to 2.84) with rosuvastatin alone and 2.06 (2.01 to 2.12) for sacubitril/valsartan alone. For atorvastatin+sacubitril/valsartan, the PRR and 95% CI were 0.95 (0.64 to 1.40). Statin+sacubitril/valsartan was not associated with a safety signal. However, rosuvastatin alone and sacubitril/valsartan alone were associated with rhabdomyolysis.