Muscle and statins: from toxicity to the nocebo effect

ABSTRACT

Introduction: Although statins have a satisfactory safety profile and are well tolerated, many statin-treated patients report muscle symptoms in clinical practice which contribute to drug discontinuation and, consequently, adverse cardiovascular outcomes.

Areas covered: This narrative review will cover the definition and prevalence of statin intolerance, the clinical spectrum of statin-associated muscle symptoms (SAMS) with special focus on patients with only mild myalgias, the complexity of statin muscle intolerance diagnosis and provide an overview on the nocebo effect of particular importance for physicians.

Expert opinion: Many patients are unable to tolerate statin therapy, with SAMS being the most common cause of statin intolerance. The reported incidence of SAMS was consistently lower in randomized placebo-controlled trials than in observational studies. These results strongly suggested that SAMS were not always due to by the pharmacologic effects of statin therapy. Convincing patients that their muscle symptoms might be due to causes other than statin treatment is sometimes difficult. Furthermore, clinicians should not prematurely discontinue statin therapy before considering other possible causes, including the nocebo effect.

KEYWORDS:

• Adverse effects
• cardiovascular disease
• statins
• statin-associated symptoms
• therapy

Article highlights

• The rate of treatment withdrawal from statins is high, mainly as a consequence of adverse effects.

• More than 90% of patients with statin intolerance could be treated with statins, and ‘complete’ intolerance to statins affects < 5% of subjects. The main approach for patients with statin intolerance should be to try not to stop statin therapy.

• Muscle symptoms are the most common side effects in patients on statins (95% of all side effects).

• When muscle symptoms are accompanied by a biochemical abnormality (rhabdomyolysis) or a histological substrate (necrotizing myositis), their diagnosis and relationship with statin therapy can be clear.

• Diagnostic dilemma arises when patients present only mild myalgia, one of the most frequent SAMS.

This box summarizes key points contained in the article.

Acknowledgments

We thank Miss Christine O’Hara for review of the English version of the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.