Wolf at the Door?
Vinaya Simha
JCEM Case Reports, Volume 3, Issue 10, October 2025, luaf183
https://doi.org/10.1210/jcemcr/luaf183
Confronted by both the overwhelming evidence on the benefits of statin therapy for cardiovascular risk reduction and the large number of patients in clinical practice who report statin “intolerance,” the exasperated clinician is almost akin to the villagers confronting the little shepherd in Aesop’s famous fable of “The Boy Who Cried Wolf.” Multiple randomized controlled trials have established the safety and efficacy of statin therapy for primary and secondary prevention, while multiple observational studies have reported a high prevalence of statin-associated muscle symptoms (SAMS) ranging from 10% to 25% and a staggering nonadherence to treatment of almost 50%. In most patients, the symptoms are mild without significant clinical sequalae, and some innovative studies have demonstrated the ability of “statin-intolerant” subjects to safely tolerate even the same statin upon retrial. Further, n-of-1 trials showed similar incidence of reported muscle symptoms when the same patients were randomly taking either a statin or a placebo, leading to the concept of a “statin-nocebo” effect being the primary driver of SAMS. Indeed, many guidelines suggest continuation of statin therapy in a different formulation or dose as the first step in managing patients with SAMS. However, we should be vigilant about rare cases of extreme muscle toxicity, which require prompt statin discontinuation and further investigations and treatment.
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