Statin associated muscle symptoms (SAMS): strategies for prevention, assessment and management

ABSTRACT

Introduction

Statins are the cornerstone for atherosclerotic cardiovascular disease risk reduction with recognized efficacy in primary and secondary prevention. Despite this, they remain underutilized due to concerns regarding adverse effects. Statin-associated muscle symptoms (SAMS) are the most frequent cause of medication intolerance and discontinuation with a prevalence estimated at 10%, regardless of causality, with the consequence of increased risk of adverse cardiovascular outcomes.

Areas covered

This clinical perspective reviews recent developments in mechanisms underlying the pathogenesis of statin myopathy, the role of the nocebo effect in perception of statin intolerance, and explores diverse components endorsed by international societies in establishing a statin intolerance syndrome. Non-statin drug alternatives that reduce low-density lipoprotein-cholesterol are also discussed, with emphasis on therapies with established effects on cardiovascular outcomes.

Expert opinion

Ultimately, a patient-centered clinical approach to managing SAMS is proposed to optimize statin tolerability, achieve guideline-recommended therapeutic goals and improve cardiovascular outcomes.

KEYWORDS:

• Lipid lowering therapy
• myalgia
• statin intolerance
• adherence
• nocebo
• placebo
• hypercholesterolemia
• atherosclerotic cardiovascular disease

Article highlights

• Statin-associated muscle symptoms (SAMS) are a common cause of goal-inhibiting statin intolerance.

• Reduced statin adherence due to SAMS increases the risk of adverse cardiovascular outcomes.

• Mechanisms underlying SAMS in most cases are poorly understood and underlie a heterogenous clinical spectrum with complex etiologies, sometimes including patient expectation of adverse effects.

• Management strategies involve a patient-centered approach, control of risk factors, and pharmacological optimization with emphasis on benefits and safety of statin therapy.

• Alternative treatment options include combining different dose statins with other lipid-lowering regimens, and use of non-statin adjuncts that are proven to reduce adverse CV events, such as ezetimibe, PCSK9 inhibitors and bempedoic acid.

• The ultimate objective is lipid goal or target achievement, which is fundamental for cardiovascular risk reduction.

Declaration of interest

RA Hegele reports consulting fees from Akcea/Ionis, Amgen, HLS Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, and Ultragenyx.

GB Mancini reports advisory board activity for Amgen, Sanofi, Esperion; Grants from Amgen, Sanofi, Astra Zeneca, and Merck.

The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

RA Hegele is supported by the Jacob J. Wolfe Distinguished Medical Research Chair, the Edith Schulich Vinet Research Chair, and the Martha G. Blackburn Chair in Cardiovascular Research. RA Hegele holds operating grants from the Canadian Institutes of Health Research (Foundation award), the Heart and Stroke Foundation of Canada (G-21-0031455) and the Academic Medical Association of Southwestern Ontario (INN21-011).