Fatal Rhabdomyolysis after Rosuvastatin Dose Modification in Acute Coronary Syndrome: A Case Report

INTRODUCTION. Following acute coronary syndrome (ACS), patients are at high risk of repeated cardiovascular accidents. They receive intensive lipid-lowering and antiplatelet therapy according to clinical recommendations. However, therapy intensification may entail increased risks of adverse drug reactions. The clinical case describes fatal rhabdomyolysis associated with high-dose rosuvastatin therapy. The risk factors of this adverse reaction have been analysed; knowing the factors can help prevent similar events in patients.
CASE REPORT. A 68-year-old patient, male, received continuous therapy with rosuvastatin 10 mg per day for 3 years with good tolerability. After the ACS, rosuvastatin dose was increased to a maximum of 40 mg per day, dual antiplatelet therapy with ticagrelor was prescribed, as well as bisoprolol, amlodipine, omeprazole, perindopril, and spironolactone. Within a month, the patient developed muscle pain and acute renal failure, with clinical and laboratory evidence confirming rhabdomyolysis. Despite intensive therapy, the patient died. An analysis was performed for genetic markers of individual rosuvastatin pharmacokinetics, showing: CYP2C9 *1*1 (normal activity), SLCO1B1 *5*15 (reduced activity for homozygous state), ABCG2 c.421 C/C (normal activity). Literature analysis of drug interaction revealed possible additional increase in rosuvastatin concentrations (up to 2.6 times) associated with ticagrelor inhibiting breast cancer resistant protein transporter activity.
CONCLUSIONS. In the present case, fatal statin-associated rhabdomyolysis developed due to two significant factors — pharmacogenetic predisposition and a significant drug-drug interaction of rosuvastatin with ticagrelor, which disrupted the functions of two carrier proteins that determine medicine bioavailability (breast cancer resistant protein) and its transport through the hepatocyte membrane (OATPB1). Pharmacogenetic testing and active monitoring of laboratory values is indicated in such patients in the first days of drug therapy for the timely diagnosis of possible complications; such situations are crucial for the prognosis in patients after ACS following high-dose statin therapy and other medicines with the potential for significant drug interactions.

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