Curriculum in CardiologyA systematic review of statin-induced muscle problems in clinical trials
Section snippets
Methods
We searched PubMed, Ovid, and Google Scholar for English-language articles reporting the results of placebo-controlled trials of statin therapy using the terms hydroxymethylglutaryl CoA reductase inhibitors, statins, muscles, muscle injury, myalgia, myopathy, and creatine kinase alone and in combinations. Studies were required to be placebo controlled, to have a minimum follow-up of 6 months, and to be published from 1990 through November 2012. We initially identified 1,012 manuscripts but
Results
Fourteen studies examined pravastatin6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19; 6, lovastatin20, 21, 22, 23, 24, 25; 6, atorvastatin26, 27, 28, 29, 30, 31; 5, simvastatin32, 33, 34, 35, 36; 5, rosuvastatin37, 38, 39, 40, 41; 5, fluvastatin42, 43, 44, 45, 46; and 1, cerivastatin (Table I).47 The age (mean ± SD) of the statin and placebo groups was 60 ± 5.5 and 60 ± 5.6 years. The mean duration of statin exposure was 3 ± 1.6 years and ranged from 0.5 to 6.1 years. Only approximately half
Discussion
We examined the study design and results of 42 clinical trials of statin therapy to determine how statin-related muscle adverse effects are evaluated and reported. Only 26 trials (Table II) reported the frequency of muscle problems, and only 1 study37 actually queried participants systematically about muscle problems. Interestingly, among those 26 studies that reported these events, 12.7% of treated and 12.4% of placebo groups reported muscle problems. Ninety-eight percent of studies did not
Conclusion
Despite these potential problems, our review suggests that the impression that statin muscle adverse effects are rare in clinical trials is correct. The incidence in treated and placebo-treated participants in the clinical trials is nearly identical and is approximately 13% of participants. Most clinical trials, however, did not solicit muscle problems, use standard definitions of muscle problems or myalgia, or report the effect of statin therapy on average CK levels. We suggest that using
Disclosures
Harsha V Ganga: none.
Hanna B Slim: none.
Paul D Thompson has received grants from GlaxoSmithKline, Genomas, Roche,Sanolfi-Aventis, Regeneron, Esperion, and Amarin; has served as a consultant for Astra Zeneca, Amgen, Regeneron, Genomas, Merck, Abbott, Runner’s World, Genzyme, Sanolfi, GlaxoSmithKline, and Esperion; has received speaking honoraria from Merck, Astra Zeneca, Abbott, GlaxoSmithKline, and Kowa; owns stock in General Electric, JA Wiley Publishing, J&J, and Abbott; and has served as
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2022, Journal of the Formosan Medical AssociationCitation Excerpt :Although myopathy and abnormal liver function are encountered occasionally, statin therapy is well tolerated and safe for most patients.103 Statin-associated muscle symptoms are the most common reported side effects, however, the risk of severe statin-induced muscle injury, including rhabdomyolysis, is very low.104 Please refer to the 2019 Taiwan Society of Lipids and Atherosclerosis Expert Consensus Statement on Statin Intolerance for the diagnosis and management of statin-related muscle and hepatic side effects.105
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2022, AtherosclerosisCitation Excerpt :Finally, perhaps the most widely recognized and yet downplayed side effect of statins is muscle damage. Myopathy occurs in ∼0.5% of patients and rhabdomyolysis in ∼0.01% [32,33], which are small but not negligible risks. As there are objective laboratory findings for these conditions their incidence is widely accepted, whereas the incidence of statin-induced myalgias is far more contentious.