Statin therapy and the risk of rhabdomyolysis in hypercholesterolemic populations
Statins remain the gold-standard pharmacologic therapy for hypercholesterolemia, but their use is occasionally limited by statin-associated muscle symptoms (SAMS), of which rhabdomyolysis is the most severe form (Dicken et al., 2022; Safitri et al., 2021). To systematically synthesize evidence published between 2010 and 2025 on the incidence, molecular mechanisms, genetic determinants, and preventive management of statin-induced rhabdomyolysis in hypercholesterolemic populations, and to identify what current evidence still leaves unresolved. A narrative literature review was conducted using Google Scholar and PubMed with the Boolean strategy ("statin*" OR "HMG-CoA reductase inhibitor*") AND ("rhabdomyolysis" OR "myopathy" OR "statin-associated muscle symptoms") AND "hypercholesterolemia". Screening followed a three-stage PRISMA-style process (identification, title/abstract screening, full-text eligibility), and included studies were appraised narratively for design, sample size, and completeness of reported outcomes, prioritizing peer-reviewed sources indexed in Scopus or Sinta and published in 2021-2025, while retaining seminal 2010-2018 randomized trials as primary sources of the quantitative incidence data. Six primary clinical studies (n = 24 to 584,784) reported rhabdomyolysis incidences ranging from 0.003% with statin monotherapy to 4.17% under high-dose oncology co-administration; risk rose sharply with fibrate co-therapy (particularly gemfibrozil), high-dose or lipophilic statins, and loss-of-function SLCO1B1 variants (Turongkaravee et al., 2021). Rhabdomyolysis attributable to statin monotherapy is rare (generally <0.1%), but risk increases materially with high-dose or lipophilic statins, fibrate co-administration, strenuous physical exertion, and genetic predisposition. Individualized risk assessment-incorporating dose selection, drug-interaction screening, and, where available, SLCO1B1 genotyping-together with creatine kinase monitoring can help preserve the cardiovascular benefit of statins while minimizing myotoxic risk.