Liver function tests statins

Patients receiving statins should have a fasting panel 4 to 8 weeks after the initial dose or dose changes. Liver function tests should be obtained at baseline and periodically thereafter based on package insert information. Some experts believe that monitoring for hepatotoxicity and myopathy should be triggered by symptoms. 

Liver function tests must be carried out before and v/ithin 1-3 months of starting treatment v/ith statins, such as fluvastatin. Liver function tests are thereafter carried out at 6-month intervals for 1 year. 

Evidence-based pharmacotherapy provides a succinct appreciation of the benefits of a drug, but rarely takes into account the patient s quality of life. Eor instance, intensive statin therapy is recommended because it reduces the incidence of cardiovascular death (odds ratio 0.86), myocardial infarction (odds ratio 0.84), and stroke (odds ratio 0.82) however, the increased risks for any adverse event (odds ratio 1.44), for abnormalities on liver function testing (odds ratio 4.48), for elevations in CK (odds ratio 9.97) and for adverse events requiring discontinuation of therapy (odds ratio 1.28) are less often taken into account by the prescriber. This example emphasises that individualisation is of the utmost importance to keep an acceptable benefit/risk ratio (Clin Ther 2007 29 253-60). The benefits of evidence-based pharmacotherapy may be obtained whenever concordance/compliance of the patient is adequate. However, concordance rate is slightly higher than 30% for chronic conditions, such as hypertension (Curr Hypertens Rep 2007 9 184-9), indicating that the patient has to be educated about the use of drugs, and therapy has to be individualised. 

Patients must be monitored carefnlly for signs of myopathy and hepatotoxicity. Elevations of transaminases as a possible pharmacodynamic effect of lipid-lowering therapy should be considered. Liver function tests (LFTs) shonld be monitored to identify possible hepatotoxicity. Statins shonld be withheld or changed if elevations in transaminases are persistently more than three times ULN or are accompanied by other signs of liver disease that might be iatrogenic. In addition, the patient mnst be adequately monitored in order to identify ... 

Pelli N, Setti M, Ceppa P, Toncini C, Indiveri F (2003) Autoimmune hepatitis revealed by atorvastatin. Eur J Gastroenterol Hepatol 15 921-924. Sniderman AD (2004) Is there value in liver function test and creatine phosphokinase monitoring with statin use Am J Cardiol 94 30F-4F. Dujovne CA (2002) Side effects of statins hepatitis versus ransaminitis myositis versus CPKitis . Am J Cardiol 89 1411-1413. 

Statins are well absorbed after administration orally, and are metabolised in the liver. They are well tolerated, the commonest adverse effect being transient, and usually minor abnormality of liver function tests in some 1% of patients. Asymptomatic elevation of muscle enzymes (creatine phos-phokinase, CPK) and myositis (with a generalised muscle discomfort) occur more rarely, but is more frequent when statins are combined with other anti-hyperlidaemic drugs such as fibrates and nicotinic acid patients should be counseled about myositis when these drugs are co-administered. Myositis is also more likely with co-administered anti-HIV protease inhibitors, and with drugs that interfere with metabolism of some statins, e.g. ciclosporin. 

The first "statin" was discovered by Endo and coworkers at Sankyo in Tokyo in 1976. After testing over 8,000 microbial extracts, they found a compound, named mevastatin (ML-236B) (Figure 9), from Penicillium citrinum which showed specific inhibition of HMG CoA reductase and functioned in vivo, lowering serum cholesterol levels. Further development of mevastatin was curtailed because inhibition of cholesterol biosynthesis was not restricted to the liver. The compound enters the lens and adrenals, where it blocks the essential biosynthesis of cholesterol. The same compound was also isolated by a team at the Beecham Research Laboratories in Brockham Park, Surrey. Whilst screening for antifungal activity, they isolated the compound, which they named compactin, from Pencillium brevicompactum, but apparently failed to recognise it as a potent inhibitor of HMG CoA reductase. 

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