Myopathy refers to any muscle disease, myalgia to muscle aches or weakness without creatine kinase elevation, and myositis includes increased creatine kinase. Rhabdomyolysis includes marked creatine kinase elevations usually with brown urine and urinary myoglobin.(1)
Statins confer statistically significant and clinically important reductions in myocardial infarction, stroke, and cardiovascular death.2 The class is well tolerated, but statins are associated with myopathy, most commonly myalgia. In randomized, double-blind, placebo-controlled trials, these conditions are similar between the statin and placebo groups. Nonetheless, in some instances the findings are sufficient for clinicians to implicate statins as a cause of these symptoms.(1)
The absolute rates of myalgia (∼5%)1 are increasing. For example, the Measuring Effects on Intima-Media Thickness: an Evaluation of Rosuvastatin trial,3 published in 2007, was a randomized, double-blind, placebo-controlled trial among 984 patients treated for 2 years with 40 mg of rosuvastatin on progression of carotid artery intima-medial thickness. This is the highest marketed dose of the most potent statin as measured by beneficial effects on low- and high-density lipoprotein cholesterol. This dose demonstrated inhibition of progression of carotid artery intima-medial thickness. Myalgia rates were 12.7% and 12.1% in the statin and placebo groups, respectively, providing reassuring data from a randomized, double-blind, placebo-controlled trial concerning statin-induced myalgia. Nonetheless, 1 in 8 patients in the placebo group reported myalgia.
In a comprehensive individual patient data meta-analysis of 90,014 subjects randomized to statins or placebo or open control, 15 cases of rhabdomyolysis occurred in 5 years, 9 in the statin group and 6 in the control group. The excess of 3 attributable to statins was half as large as the 6 resulting from the standard use of cardiovascular drugs.
It is tempting to speculate that the perceptions by clinicians of high rates of myopathy among patients treated with statins may be due, at least in part, to direct to consumer advertising by the various drug manufacturers. To comply with US federal regulations,4 such advertisements may state benefits but also must clearly articulate potential risks. Presumably, such direct to consumer advertising must increase sales, at least in the short run, but in the long run may contribute to increasing difficulties for clinicians trying to implement the US federal guidelines for more widespread and intensive statin therapy.(5) It also is tempting to speculate that nonbranded public service announcements could emphasize that cardiovascular disease is the leading killer in the United States and is becoming so worldwide.(6) Further, it could be emphasized that therapeutic lifestyle changes and adjunctive drug therapies, particularly statins, may reduce premature morbidity and mortality from cardiovascular disease.
A final suggestion to fellow academicians is to emphasize to the media that the current life expectancy in the United States is the result of not only improvements by patients in their risk factors for cardiovascular disease, but also the substantial contributions by clinicians, including earlier diagnosis and more aggressive treatment. Despite increasingly formidable challenges in the US health care system, clinicians are perhaps doing more good for more patients than ever before.
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– Charles H. Hennekens, MD
This article was originally published in January 2009 issue of The American Journal of Medicine.
