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Safety and efficacy of statin therapy


The 2013 ACC/AHA guidelines on blood cholesterol management were a major shift in the delineation of the main patient groups that could benefit from statin therapy and emphasized the use of higher-intensity statin therapies. In 2016, an expert consensus panel from the ACC recommended the use of nonstatin therapies (ezetimibe and PCSK9 inhibitors) in addition to maximally tolerated statin therapy in individuals whose LDL-cholesterol and non-HDL-cholesterol levels remained above certain thresholds after statin treatment. Given the substantial benefits of statin therapies in both primary and secondary prevention of cardiovascular disease, their long-term safety has become a concern. The potential harmful effects of statin therapy on muscle and liver have been known for some time, but new concerns have emerged regarding the risk of new-onset diabetes mellitus, cognitive impairment and haemorrhagic stroke associated with the use of statins and the risks of achieving very low levels of LDL cholesterol. The increased media attention on the adverse events associated with statins has unfortunately led to statin therapy discontinuation, nonadherence to therapy or concerns about initiating statin therapy. In this Review, we explore the safety of statin therapy in light of the latest evidence and provide clinicians with reassurance about the safety of statins. Overwhelming evidence suggests that the benefits of statin therapy far outweigh any real or perceived risks.

Key points

  • Moderate-intensity and high-intensity statin therapy has demonstrated benefits in reducing the risk of atherosclerotic cardiovascular disease in both primary and secondary prevention.

  • The most commonly reported adverse effects of statins are statin-associated muscle symptoms (SAMS), but whether these symptoms are caused by statin pharmacological effects or by nocebo effects is controversial.

  • The clinical tool SAMS-Clinical Index (SAMS-CI) might help clinicians to assess SAMS.

  • Although hepatotoxicity has been a previous concern when using statin therapy, data suggest that statins are safe and that levels of liver enzymes do not need to be checked routinely.

  • Other known adverse effects of statins include a small increase in the risk of diabetes mellitus and a possible increase in haemorrhagic stroke in patients who have had a previous stroke.

  • Although concerns have been raised about reaching very low levels of LDL cholesterol, data from trials on PCSK9 inhibitors suggest that low LDL-cholesterol levels are safe.

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Fig. 1: Clinical benefits and potential adverse effects of statin therapy.


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Review criteria

We conducted a literature search using Medline, PubMed and Embase and limited the search to the years 2000–2017. Search terms included “statin adverse effects”, “statin safety”, “statin side effects” and “statin intolerance”. In addition, search terms related to specific target organs and adverse events were also used, including “statin AND muscle, diabetes, glucose, cognitive function and stroke”. Publications were fully reviewed if the abstract suggested that the study was relevant and used only human data.

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Both authors researched data for the article, contributed to the discussion of content, and wrote, reviewed and edited the manuscript before submission.

Corresponding authors

Correspondence to Bhavin B. Adhyaru or Terry A. Jacobson.

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Competing interests

T.A.J. is a consultant for Amgen and Regeneron/Sanofi. B.B.A. declares no competing interests.

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Statin-associated muscle symptoms

(SAMS). Muscle symptoms that are the most prevalent adverse effect reported with statin therapy.

Statin intolerance

A clinical syndrome characterized by the inability to tolerate multiple statins with either objectionable symptoms or abnormal laboratory determinations that are temporally related to statin treatment and reversible upon statin discontinuation but reproducible by rechallenge.

Creatine kinase

An enzyme that is found in skeletal muscle, the heart, and the brain, and increases in the blood due to muscle injury, inflammation or necrosis of skeletal or heart muscle.


A condition involving muscle aches, stiffness, soreness, tenderness or cramps.


A rare, life-threatening condition, characterized by the rapid destruction of skeletal muscle typically with creatine kinase levels >10 times the upper limit of normal and which often leads to acute renal failure.

Statin-induced necrotizing autoimmune myopathy

(SINAM). A rare, immune-mediated myopathy characterized by proximal muscle weakness, muscle necrosis with markedly elevated creatine kinase levels, and the presence of autoantibodies to hydroxyl-methyl-glutaryl-coenzyme A reductase, in which muscle symptoms persist despite statin discontinuation.

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Adhyaru, B.B., Jacobson, T.A. Safety and efficacy of statin therapy. Nat Rev Cardiol 15, 757–769 (2018).

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