Statins Are "Remarkably Safe," Says New Review

June 11, 2007 — A new review of the safety of statins has concluded that these drugs are well tolerated, with their main adverse effects — myopathy and rhabdomyolysis — occurring very rarely at standard doses.
"With a few caveats and while awaiting good quality randomized data for the newer drugs, statins seem to be a remarkably safe group of drugs when used at their usual doses," the author, Dr Jane Armitage (University of Oxford, UK), concludes.
The review, published online in The Lancet on June 7, includes all papers published between 1985 and 2006 on the safety, efficacy, and side effects of statins. Armitage notes that since statins were first approved in 1987, their ability to reduce the risks of vascular death, non-fatal MI, stroke, and the need for arterial revascularization has been shown by several large, high-quality randomized trials. But she adds that hopes that statins might protect against fractures, dementia and macular degeneration have not been supported by evidence from randomized trials.
Myopathy
Armitage says the only well-documented, consistent adverse effects associated with statins are muscle toxicity, including myopathy and rhabdomyolysis, and effects on liver enzymes. She states that all statins occasionally cause myopathy which could progress to rhabdomyolysis but she estimates that myopathy occurs in fewer than one in 10,000 patients at standard doses of statins; and while the risk increases with higher statin doses, it remains very low with atorvastatin 80 mg. Myopathy or rhabdomyolysis are usually reported in association with concomitant use of interacting drugs (especially fibrates), the review notes, adding that this side-effect is most likely to occur within a few months of starting statin treatment, or of increasing the dose, although some cases have been reported even after some years of apparently stable statin treatment, usually as the result of starting an interacting drug.
Armitage points out that muscle pain is common in middle-aged patients (and often believed to be due to the drug because of product warnings), but is, nevertheless, unlikely to be due to statin treatment. Measurement of creatine kinase in such patients can exclude myopathy and allow safe continuation of treatment, she says. Importantly, any risks of myopathy and rhabdomyolysis can be kept to a minimum by knowledge of potential drug interactions and the vulnerability of particular groups of patients, she adds.
Transaminase Increases
The review reports that a small percentage of patients taking statins experience an increase in liver enzymes (in particular, alanine and aspartate transaminases), generally seen in the first 6 months of treatment. These are asymptomatic, are reversible on stopping the statin treatment or with dose reduction, and there is no convincing evidence from the statin trials that increases in either transaminase are associated with liver damage, Armitage writes. She adds that the effect on transaminases seems to be dose dependent, and effects on other liver enzymes and bilirubin also emerge with higher doses, but unlike with myopathy, the effects might be because of a greater fall in LDL cholesterol. But even at high doses, these liver enzyme increases have not been associated with hepatitis or liver failure.
She notes that routine monitoring of liver function after starting statin treatment is no longer recommended for simvastatin, pravastatin, or lovastatin up to 40 mg daily, but remains recommended for the other statins and higher doses. If transaminases are more than three times the upper limit of normal in an asymptomatic patient with no other liver abnormalities, the enzymes should be checked within a week and statin treatment stopped temporarily if alanine transaminase is still at this level. Increases to between two to three times the upper limit of normal in an asymptomatic patient necessitate monitoring, but will often resolve while on treatment.
The review also examines the safety of statins in several vulnerable groups. It says that no adjustment of dosage is needed for the elderly, since people aged up to 80 years were recruited in the various trials, but that the very elderly may be at increased risk of myopathy. It also reports that there is no evidence to suggest people consuming excess alcohol are at greater risk of side effects from statin use, although many such people were excluded from statin trials. Warfarin users may need to adjust the amount of the anticoagulant when statin treatment begins and again when it ends, it adds.
Lancet. Published online June 7, 2007.