Strategies to Preserve the Use of Statins in Patients With Previous Muscular Adverse Effects

Kurt M. Reinhart; J. Andrew Woods


Am J Health Syst Pharm. 2012;69(4):291-300. 

In This Article

Abstract and Introduction


Purpose The published evidence on strategies for avoiding the discontinuation of statin therapy due to muscular adverse effects is reviewed.
Summary Statin medications are a cornerstone of the prevention and treatment of coronary heart disease, but about 20% of treated patients develop myalgia or other muscle-related adverse effects that can lead to the discontinuation of statin use. As there are no consensus guidelines or firm practice recommendations on continuing or reinitiating statin therapy in patients who experience statin-related muscular adverse effects, a literature search was conducted to evaluate a variety of strategies that have been studied. The search results indicated that the most widely used strategies are (1) alternative statin dosing, (2) co-enzyme Q10 supplementation, (3) vitamin D supplementation, (4) conversion to red yeast rice (RYR) therapy, and (5) conversion to a different statin. While positive results in some patients have been reported with all of the strategies reviewed, the available evidence is insufficient to support the routine use of any of the strategies in clinical practice. In particular, the use of RYR, which contains a naturally occurring statin, is not recommended due to limited and inconsistent study results and uncertainty about the contents of commercially available RYR products.
Conclusion In patients intolerant to statin therapy due to myalgia or other muscular adverse effects, strategies such as alternative statin dosing schedules, coenzyme Q10 or vitamin D supplementation, and conversion to RYR or an alternative statin may allow some patients to continue to receive the benefits of lipid-lowering therapy.


Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, are a key component of the treatment and prevention of coronary heart disease (CHD). In patients with diagnosed CHD, statins reduce the number of subsequent coronary events and the need for revascularization and improve overall survival.[1] In patients without established CHD, lipid-lowering therapy with statins reduces the risk of myocardial infarction and death from cardiovascular causes, even in some patients without dyslipidemia.[2,3] Given that the lifetime risk of CHD at age 40 years approaches 50% in men and 33% in women,[4] the importance of statin use in reducing the morbidity and mortality associated with CHD is quite evident. Unfortunately, some patients need to discontinue statin therapy due to adverse effects and may not realize those benefits. Although generally considered to be well tolerated, statin therapy is discontinued in about 10% of patients after 1 year of treatment and in about 28% of patients after 4 years; about 39% of those patients discontinue statin use due to adverse effects.[5]

Myalgia is a poorly understood adverse effect of statins and a frequent cause of treatment discontinuation. While rates of myalgia in randomized controlled trials of statins have been low, these trials have used inconsistent definitions of myalgia, systematically excluded subjects at higher risk for developing muscle symptoms, and focused on more serious muscular adverse effects such as myositis and rhabdomyolysis.[6,7] Studies designed specifically to evaluate the rate of statin-related myalgia, however, have revealed that approximately 22% of patients taking statins report some degree of musculoskeletal pain.[7] While it may be difficult to differentiate statin- induced myalgia from muscle pain due to other causes, the very presence of myalgia in patients receiving statins may influence either the patient or provider to discontinue treatment and rely on an alternative agent for the treatment of hyperlipidemia or coronary disease, which may not offer the same benefits in terms of mortality risk reduction. Accordingly, any strategy capable of preventing repeat myalgia in these patients will help enable their continued use of statin medication and help lower the morbidity and mortality associated with CHD. There are, however, no well-accepted guidelines or recommendations on maintaining the use of a statin in these situations. In this article, we systematically review strategies that have been studied, provide recommendations for their implementation, and identify areas for further research.

When reviewing the literature on statin-related muscular adverse effects, it is important to clarify the various terminologies. The term myopathy can indicate any disease of the muscles, whereas myalgia refers to a muscle ache or weakness without concomitant elevations of enzyme levels (particularly creatine kinase), and myositis denotes myalgia accompanied by elevated creatine kinase.[8] The most serious adverse event is rhabdomyolysis, wherein the muscle damage is severe and kidney damage may result. These definitions may vary depending on the source.[8] The information presented in this systematic review is specific to myopathy and myalgia, and the treatment strategies discussed are not appropriate for patients with more severe muscular disease.


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