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

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).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.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.ISRCTN48489393The HMG-CoA reductase inhibitor simvastatin is widely used to lower LDL cholesterol and reduce cardiovascular risk[1]. The substantial reductions in cardiovascular morbidity and mortality produced by lowering blood cholesterol with simvastatin were established first in hypercholesterolaemic patients with coronary heart disease (CHD)[2], and subsequently by the Heart Protection Study (HPS) and other trials, in a broad range of high risk patients with and without hypercholesterolaemia or CHD [3-7]. Large long-term randomized trials can provide valuable information on clinically relevant adverse effects of drugs that are too uncommon to be evaluated in the smaller, relatively short-term, trials upon which regulatory approval is typically based. The tolerability of simvastatin early in HPS has been reported[8], and the safety further summarised in the first report of results[3]. The lack of any detectable effect of simvastatin on the risk of non-cardiovascular mortality, haemorrhagic stroke, cancer, respiratory and neurological morbidi