Wednesday, August 12, 2009
statines
pubmed gastro-enterology 12 ? augustus 09
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.
Background
The 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 morbidity, and the lack of hazard in patients with diabetes or heart failure, as well as those with low blood cholesterol, have been reported in subsequent papers.[4,5,9,10] In this paper, we provide further detail about the effects on muscle and liver adverse events in HPS.
Since their introduction in the 1980s, statins have been recognised to have occasional adverse effects on muscle and liver, with the former of greater clinical importance. Few drugs have toxic effects on skeletal muscle, but all statins occasionally cause myopathy.[11-13] In this context, myopathy is generally defined as unexplained muscle pain or weakness accompanied by a creatine kinase (CK) level >10 times the upper limit of normal (ULN).[11,14] Rhabdomyolysis is a severe form of myopathy (typically with CK >40 × ULN) that may require the patient to be hospitalised, often associated with myoglobinuria that can lead to acute renal failure and death. Though rare with all currently marketed statins, this adverse effect has been the focus of increased concern as a result of the withdrawal of cerivastatin by its manufacturer in 2001 due to a high incidence of rhabdomyolysis.[15]
Treatment with lipid lowering therapy, including statins, tends to increase hepatic transaminases, but clinical hepatitis is uncommon during statin therapy.[16,17] Routine monitoring of liver function has been recommended in the prescribing information for all statins, but its usefulness has subsequently been questioned.[16,18] The size, duration and placebo control of HPS provides the opportunity to assess clinical and biochemical adverse effects on muscle and liver during treatment with simvastatin 40 mg daily, and to use this information to evaluate the value of routine monitoring of liver function tests.
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.
Background
The 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 morbidity, and the lack of hazard in patients with diabetes or heart failure, as well as those with low blood cholesterol, have been reported in subsequent papers.[4,5,9,10] In this paper, we provide further detail about the effects on muscle and liver adverse events in HPS.
Since their introduction in the 1980s, statins have been recognised to have occasional adverse effects on muscle and liver, with the former of greater clinical importance. Few drugs have toxic effects on skeletal muscle, but all statins occasionally cause myopathy.[11-13] In this context, myopathy is generally defined as unexplained muscle pain or weakness accompanied by a creatine kinase (CK) level >10 times the upper limit of normal (ULN).[11,14] Rhabdomyolysis is a severe form of myopathy (typically with CK >40 × ULN) that may require the patient to be hospitalised, often associated with myoglobinuria that can lead to acute renal failure and death. Though rare with all currently marketed statins, this adverse effect has been the focus of increased concern as a result of the withdrawal of cerivastatin by its manufacturer in 2001 due to a high incidence of rhabdomyolysis.[15]
Treatment with lipid lowering therapy, including statins, tends to increase hepatic transaminases, but clinical hepatitis is uncommon during statin therapy.[16,17] Routine monitoring of liver function has been recommended in the prescribing information for all statins, but its usefulness has subsequently been questioned.[16,18] The size, duration and placebo control of HPS provides the opportunity to assess clinical and biochemical adverse effects on muscle and liver during treatment with simvastatin 40 mg daily, and to use this information to evaluate the value of routine monitoring of liver function tests.
# posted by roodbont @ 2:24 PM 
