Clinical question
What are the effects of statins on muscles?
Bottom line
Statins increase the risk of muscle symptoms (pain, cramps, weakness) in the first year of use, from 14.0% (placebo) to 14.8%, but are similar to placebo after 1 year. Only 1 patient-reported muscle symptom in 15 is due to the statin. Statins may increase muscle symptoms with creatine kinase rising to 10 times normal levels for 1 in about 3000 patients over placebo.
Evidence
Seven systematic reviews (11 to 135 RCTs; N=18,192 to 192,977) from the past 5 years examine this.1-7 We focus on the most recent (23 RCTs; 154,664 patients over 4.3 years).1 Results are statistically significant unless indicated.
Any muscle symptoms for statin versus placebo …
- Anytime: 27.1% versus 26.6% (placebo).1
— Within the first year: 14.8% versus 14.0%, number needed to harm of 125.
— After the first year: 14.8% versus 15.0% (not statistically different).
- Other systematic reviews2-7 had similar but not statistically different results for myalgia,5 those 65 and older,4 and intensity versus placebo.2 No difference by statin type,3 lipophilic or hydrophilic statins,6 or age group.1,5,6
Any muscle symptoms, more- versus less-intense statin …
Creatine kinase level more than 10 times the upper limit of normal (myopathy): 0.077% versus 0.044% (placebo).1
Rhabdomyolysis: 3 systematic reviews4,5 found no difference.
Discontinuation for muscle symptoms2,4 or any adverse event4,5,7 was not statistically increased.
Two large n-of-1 trials (60 to 200 patients with previous statin intolerance due to muscle symptoms) randomized to 3 to 4 cycles of about 4 to 8 weeks each of statin,8,9 placebo,8,9 and no pill.8
Context
Implementation
Statins are the most effective lipid-lowering drugs to prevent cardiovascular (CV) diseases, with a relative risk reduction of 25% to 35% for CV events and about 10% for mortality.10,11 For nonsevere muscle symptoms possibly caused by a statin, other causes should be excluded.12 If none is identified, stop the statin and try a rechallenge in a few weeks with the same dose, a lower dose, a different statin, or alternate-day dosing, as most patients will tolerate rechallenge.8-10,12 Non-statin therapies appear to have fewer CV benefits and no mortality effect and should be considered only if statin intolerance is severe or unmanageable.10,11
Notes
Tools for Practice articles in CFP are adapted from peer-reviewed articles at http://www.toolsforpractice.ca and summarize practice-changing medical evidence for primary care. Coordinated by Dr G. Michael Allan and Dr Adrienne J. Lindblad, articles are developed by the Patients, Experience, Evidence, Research (PEER) team and supported by the College of Family Physicians of Canada and its Alberta, Ontario, and Saskatchewan Chapters. Feedback is welcome at toolsforpractice{at}cfpc.ca.
Footnotes
Competing interests
None declared
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La traduction en français de cet article se trouve à https://www.cfp.ca dans la table des matières du numéro de mai 2023 à la page e108.
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