Fibrates in the prevention of cardiovascular disease in patients with type 2 diabetes mellitus: meta-analysis of randomised controlled trials

To assess the impact of lipid lowering treatment with fibrates on cardiovascular endpoints in patients with type 2 diabetes mellitus.

Treatment of hypercholesterolemia in patients with primary biliary cirrhosis might be more beneficial than indicated

Cholesterol circulating levels are elevated in most of the patients with primary biliary cirrhosis. This review questions whether hypercholesterolaemia represents a cardiovascular risk in primary biliary cirrhosis and whether it should be treated. The published evidence indicates that hypercholesterolaemia in patients with primary biliary cirrhosis should be considered a cardiovascular risk factor only when other factors are present. Ursodeoxycholic acid the standard treatment of primary biliary cirrhosis improves the cholestasis and hereby lowers circulating levels of cholesterol. Primary biliary cirrhosis is not a contraindication to prescribe statins or fibrates to these patients. Interestingly, these two classes of drugs have been shown to improve not only the lipid profile but also the liver tests. In particular fibrates have been found to normalize liver tests in patients responding incompletely to ursodeoxycholic acid. Statins as well as fibrates possess specific anti-inflammatory properties which may be beneficial in primary biliary cirrhosis. In conclusion, hypercholesterolaemia in the absence of other cardiovascular risk factors does not require specific therapeutic intervention in patients with primary biliary cirrhosis. However, statins as well as fibrates seem to have beneficial effects on the primary biliary cirrhosis itself and deserve formal testing within clinical trials.

Rhabdomyolysis in association with simvastatin and amiodarone

OBJECTIVE To report a case of severe myopathy associated with concomitant simvastatin and amiodarone therapy. CASE SUMMARY A 63-year-old white man with underlying insulin-dependent diabetes, recent coronary artery bypass surgery, and postoperative hemiplegia was treated with aspirin, metoprolol, furosemide, nitroglycerin, and simvastatin. Due to recurrent atrial fibrillation, oral anticoagulation with phenprocoumon and antiarrhythmic treatment with amiodarone were initiated. Four weeks after starting simvastatin 40 mg/day and 2 weeks after initiating amiodarone 1 g/day for 10 days, then 200 mg/day, he developed diffuse muscle pain with generalized muscular weakness. Laboratory investigations revealed a significant increase of creatine kinase (CK) peaking at 40 392 U/L. Due to a suspected drug interaction of simvastatin with amiodarone, both drugs were stopped. CK normalized over the following 8 days, and the patient made an uneventful recovery. An objective causality assessment revealed that the myopathy was probably related to simvastatin. DISCUSSION Myopathy is a rare but potentially severe adverse reaction associated with statins. Besides high statin doses, concomitant use of fibrates, defined comorbidities, and concurrent use of inhibitors of cytochrome P450 are important additional risk factors. This is especially relevant if statins predominantly metabolized by CYP3A4 are combined with inhibitors of this isoenzyme. Amiodarone is a potent inhibitor of several different CYP isoenzymes, including CYP3A4. CONCLUSIONS Avoiding the concomitant use of drugs with the potential to inhibit CYP-dependent metabolism (eg, amiodarone) or elimination of statins may decrease the risk of statin-associated myopathy. Alternatively, if drug therapy with a potent CYP inhibitor is inevitable, choosing a statin without relevant CYP metabolism (eg, pravastatin) should be considered.