Research article

Effects of simvastatin 40 mg daily on muscle and liver adverse effects in a 5-year randomized placebo-controlled trial in 20,536 high-risk people

MRC/BHF Heart Protection Study Collaborative Group

Heart Protection Study, Clinical Trial Service Unit & Epidemiological Studies Unit, Richard Doll Building, Oxford University, Old Road Campus, Roosevelt Drive, Headington, Oxford, OX3 7LF, UK

author email corresponding author email

BMC Clinical Pharmacology 2009, 9:6doi:10.1186/1472-6904-9-6

Published:	31 March 2009

Abstract

Background

Simvastatin reduces cardiovascular mortality and morbidity but, as with other HMG-CoA reductase inhibitors, can cause significant muscle toxicity and has been associated with elevations of liver transaminases.

Methods

Muscle and liver adverse effects of simvastatin 40 mg daily were evaluated in a randomized placebo-controlled trial involving 20,536 UK patients with vascular disease or diabetes (in which a substantial reduction of cardiovascular mortality and morbidity has previously been demonstrated).

Results

The excess incidence of myopathy in the simvastatin group was < 0.1% over the 5 years of the trial, and there were no significant differences between the treatment groups in the incidence of serious hepatobiliary disease.

Conclusion

Among the many different types of high-risk patient studied (including women, older individuals and those with low cholesterol levels), there was a very low incidence (< 0.1%) of myopathy during 5 years treatment with simvastatin 40 mg daily. The risk of hepatitis, if any, was undetectable even in this very large long-term trial. Routine monitoring of liver function tests during treatment with simvastatin 40 mg is not useful.

Trial Registration

ISRCTN48489393