Atorvastatin/Bezafibrate and Intensive Physical Exercise–induced Rhabdomyolysis in a Hyperlipidemic Patient in Secondary Prevention

Background Cardiovascular diseases are a major global health concern, and statin therapy plays a pivotal role in both primary and secondary prevention. Statin–associated muscle symptoms are relatively common, whereas rhabdomyolysis remains a rare but potentially life–threating complication. Case presentation We report the case of a 64–year–old male patient with a history of myocardial infarction and mixed hyperlipemia (total cholesterol 280 mg/dL and triglycerides 350 mg/dL) He was initially treated with atorvastatin 40 mg/dL, with normal creatine kinase (CK) levels. However, after approximately 4 years of treatment, the patient began intensive weight training and subsequently developed marked CK elevation (up to 11,645 U/L). He was hospitalized with a diagnosis of rhabdomyolysis, and lipid–lowering therapy was switched to bezafibrate 400 mg/day. After 5 months, in August 2007, he was readmitted for a milder episode of rhabdomyolysis (CK 4,300 U/L). From September 2007, treatment consisted of colesevelam 625 mg six tablets/day, omega–3 fatty acids 4 g/ day, and ezetimibe 10mg/day. In March 2017, alirocumab 75 mg every other week was initiated, achieving LDL–C levels ‹ 55 mg/dL. In July 2020, a severe episode of rhabdomyolysis occurred following participation in an equestrian competition (CK 16,686 U/L). CK values decreased to ‹ 500 U/L after 10 days of aggressive intravenous hydration. In September 2020, the alirocumab dose was increased from 75mg to 150mg, in order to counteract an apparent loss of lipid–lowering efficacy. A muscle biopsy perfomed in March 2021 yielded normal results. In August 2023, the patient experienced another episode of rhabdomyolysis (CK 5,000 U/L), which was managed at home with intensive oral hydration. In February 2024, bempedoic acid 180 mg/day was added, resulting in a successful LDL–C reduction, to 41 mg/dl. Conclusion Individual susceptibility to lipid lowering treatments, particularly statins and fibrates, should be carefully evaluated, especially in patients receiving combination therapy and engaging in intense physical activity. In this case, PCSK9 inhibitors, ezetimibe and bempedoic acid provided a safe and effective lipid–lowering strategy without further severe muscle toxicity.