Elsevier

Progress in Cardiovascular Diseases

Volume 75, November–December 2022, Pages 40-48
Progress in Cardiovascular Diseases

Statin associated muscle symptoms: An update and review

https://doi.org/10.1016/j.pcad.2022.11.010Get rights and content

Abstract

Statin therapy has been shown to have a significant effect on lowering of low-density lipoprotien cholesterol (LDL-C) levels. This subsequently results in cardiovascular (CV) benefit through reduction in major adverse CV disease (CVD) events and overall mortality. Although there is well proven clinical benefit, statin therapy may be discontinued in some patients, and the most common cause for discontinuation is concern for statin-associated muscle symptoms. However, the data on the true prevalence of these symptoms is mixed and continued studies are showing that the symptoms may be less prevalent than previously believed. With statin-associated muscle symptoms being the most common reason for a patient to not be on statin therapy, it is important for physicians to understand how to evaluate for and manage these symptoms. This manuscript provides an overview of statin associated muscle symptoms so that physicians may be able to better manage patients on statin therapy and continue to use these medications when indicated to best reduce future risk of CVD for patients.

Introduction

Statin therapy is one of the primary modalities for addressing dyslipidemia and reducing the risk of atherosclerotic cardiovascular (CV) disease (CVD;ASCVD). This results from evidence that statins have strong efficacy in not only improving the cholesterol profile, but also in reducing negative CVD outcomes. Studies have shown that each 1 mmol/L (approximately 39 mg/dL) reduction in low-density lipoprotein cholesterol(LDL-C) is associated with a 25% reduction in major adverse CVD events during each year (after the first) that it continues to be taken.1 There is a similar correlation with mortality, specifically with a 20% reduction in coronary artery disease-related deaths and a 10% reduction in all-cause mortality over a 5-year period.1 When looking more specifically at intensifying statin therapy, a further reduction in LDL-C by 0.5 mmol/L is correlated with an additional 15% reduction in the rate of deaths. Overall, this relates to a 28% risk reduction for every 1 mmol/L decrease in LDL-C.1 Much of this data was obtained from studies done in large cohorts with variable underlying risk levels for ASCVD, but pooled cohorts of patients with higher risk have shown similar, if not stronger results for the benefit of statin therapy.1 These data emphasize the importance of initiating and appropriately titrating the dose of statin therapy when indicated.

Despite the aforementioned data, a significant amount of the population who would benefit from statin therapy is either not on an appropriate dose, or not taking the medication at all. Specifically, discontinuation rates of statins within the first two years of therapy have been shown to approach 75%.2 The primary reason for patients not being on appropriate statin therapy is due to statin associated muscle symptoms (SAMS).2 SAMS are broadly defined as symptoms of muscle discomfort or pain associated with statin therapy. While some patients may not be able to tolerate appropriate statin therapy due to these muscle symptoms, many of these symptoms are either unrelated to statin therapy or can be addressed and managed through multiple means without having to discontinue statin therapy. This manuscript aims to provide an overview of the information that is currently known about statin therapy and SAMS. Through this information, physicians will be better able to evaluate and manage SAMS so that a greater number of patients may receive the CV benefits that statin therapy can provide.

Section snippets

Prevalence of SAMS

A major question surrounding SAMS is the true prevalence within society. This has been difficult to determine, as there are significant discrepancies between data from observational studies and registry reviews when compared to that of randomized controlled trials.3 While large scale observational studies and registry reviews have shown an incidence of SAMS ranging from 10 to 29%, lack of placebo comparisons prevents the ability to establish a causal relationship with statin therapy.2

Conclusion

Statins are the mainstay of therapy for primary and secondary prevention of cardiovascular disease due to their proven ability to reduce low-density lipoprotein cholesterol (LDL-C) and reduce cardiovascular morbidity and mortality. However, despite their proven benefits they are underutilized due to the perceived prevalence of statin associated muscle symptoms (SAMS), the primary reason that most patients discontinue statin therapy or choose not to start the medication. This perception has

Declaration of Competing Interest

None.

References (62)

  • R.S. Rosenson et al.

    The National Lipid Association’s muscle safety expert panel. An ASSESSMENT by the statin muscle safety task force: 2014 update

    J Clin Lipidol

    (2014)
  • G.B. Mancini et al.

    Diagnosis, prevention, and management of statin adverse effects and intolerance: CanadianWorking Group Consensus update

    Can J Cardiol

    (2013)
  • P.M. Moriarty et al.

    Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: the ODYSSEY ALTERNATIVE randomized trial

    J Clin Lipidol

    (2015)
  • M.K. Cheeley et al.

    NLA scientific statement on statin intolerance: a new definition and key considerations for ASCVD risk reduction in the statin intolerant patient

    J Clin Lipidol

    (2022)
  • W.M. Mampuya et al.

    Treatment strategies in patients with statin intolerance: the Cleveland Clinic experience

    Am Heart J

    (2013)
  • E.S. Stroes et al.

    Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, aetiology and management

    Eur Heart J

    (2015)
  • T.T. Abd et al.

    Statin-induced myopathy: a review and update

    Expert Opin Drug Saf

    (2011)
  • L.R. Brunham et al.

    Role of genetics in the prediction of statin-associated muscle symptoms and optimization of statin use and adherence

    Cardiovasc Res

    (2018)
  • C. Bucsa et al.

    Drug-drug interactions of statins potentially leading to muscle-related side effects in hospitalized patients

    Rom J Intern Med

    (2015)
  • K. Kellick

    Organic ion transporters and statin drug interactions

    Curr Atheroscler Rep.

    (2017)
  • E.S. Istvan et al.

    Structural mechanism for statin inhibition of HMG-CoA reductase

    Science

    (2001)
  • C. Stancu et al.

    Statins: mechanism of action and effects

    J Cell Mol Med

    (2001)
  • J.K. Liao et al.

    Pleiotropic effects of statins

    Annu Rev Pharmacol Toxicol

    (2005)
  • N.C. Ward et al.

    Statin toxicity

    Circ Res

    (2019)
  • M. Apostolopoulou et al.

    The role of mitochondria in statin-induced myopathy

    Eur J Clin Invest

    (2015)
  • M. Niemi

    Transporter pharmacogenetics and statin toxicity

    Clin Pharmacol Ther

    (2010)
  • E. Link et al.

    SLCO1B1 variants and statin-induced myopathy—a genomewide study

    N Engl J Med

    (2008)
  • MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial

    The Lancet

    (2002)
  • P.M. Ridker et al.

    Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein

    New England Journal of Medicine

    (2008)
  • B.C. Fellström et al.

    Rosuvastatin and cardiovascular events in patients undergoing hemodialysis

    N Engl J Med

    (2009)
  • J.R. Crouse et al.

    Effect of Rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical Atherosclerosis The METEOR trial

    JAMA

    (2007)
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