Long-term safety of statin-fibrate combination treatment in the management of hypercholesterolaemia in patients with coronary artery disease.

Abstract

Interventions-Twice daily lipid lowering treatment was given, with the fibrate administered in the morning (either bezafibrate 400 mg (n = 101) or fenofibrate 200 mg (n = 1)) and the statin in the evening (either simvastatin 10 mg (n = 23), 20 mg (n = 72), or 40 mg (n = 2) or pravastatin 10 mg (n = 1) or 20 mg (n = 4)). Treatment continued for 1 (n = 9), 2 (n = 58), or 3 (n = 35) years. Main outcome measures-Selected laboratory variables (total cholesterol concentration and liver (aspartate transaminase (AST)) and muscle enzyme (creatine kinase (CK)) activities) and documented symptomatology. Results-A mean (SD) total cholesterol concentration of 5 2 (0.8) mmolIl was achieved after combined treatment for 1 year which was maintained at annual follow up. Over a maximum 3 year follow up no patient reported myalgic symptoms and none had a measured CK activity > 10 times above nomal. Four men on a simvastatinbezafibrate combination had a CK activity rise to less than three times normal. Fourteen patients with a negative history of alcohol excess (consumption < 21 units/week) had borderline raised AST values. Conclusions-Statin-fibrate combination treatment for up to 3 years in a cohort of patients with coronary artery disease was not associated with serious disturbances in biochemical markers of muscle or liver function. (Br Heart J 1995;74:14-17)

Atorvastatin and Micronized Fenofibrate Alone and in Combination in Type 2 Diabetes With Combined Hyperlipidemia

“…This regimen has not been widely adopted because of the concern about side effects, mainly myopathy, reported with the lovastatingemfibrozil combination (20). This has not been confirmed by studies using other statin-fibrate combinations (12)(13)(14)(15)(16)(17)(18)(19). The recently reported problems with cerivastatin, when combined with gemfibrozil, seem to be related mainly to the toxicity of cerivastatin, because most deaths due to myopathy-rhabdomyolysis reported in the U.S. were associated with monotherapy rather than with combination therapy.…”

“…An effective therapeutic approach of CHL in nondiabetic patients is a statinfibrate combination (12)(13)(14)(15)(16)(17)(18)(19). This regimen has not been widely adopted because of the concern about side effects, mainly myopathy, reported with the lovastatingemfibrozil combination (20).…”

“…Recent studies (9,10) showed that statin or fibrate monotherapies can improve the lipid profile in patients with type 2 diabetes and CHL; however, these affect differe n t a s p e c t s o f l i p o p r o t e i n ( L P ) metabolism. Hence, it is difficult to modify the lipid profile of patients with type 2 diabetes and CHL using monotherapy with either a statin or a fibrate, according to the recent suggestions of the American Diabetes Association (ADA) (11).An effective therapeutic approach of CHL in nondiabetic patients is a statinfibrate combination (12)(13)(14)(15)(16)(17)(18)(19). This regimen has not been widely adopted because of the concern about side effects, mainly myopathy, reported with the lovastatingemfibrozil combination (20).…”

Combined therapy in the treatment of dyslipidemia

“…This combination can be prescribed to patients who are not receiving cyclosporines, protease inhibitors or other drugs metabolized through cytochrome P450 (especially 3A4) [92]. In such a combination fibrates should preferably be taken in the morning and statins at evening to minimise peak dose concentrations [93]. Based on previously mentioned data, avoidance of gemfibrozil addition to a statin regimen is advised.…”

HMG CoA reductase‐inhibitor‐related myopathy and the influence of drug interactions

“…Drug interactions also significantly increase the risk. For example, the incidence of myopathy increases to 1% if the HMG CoA reductase inhibitor, lovastatin, is combined with nicotinic acid or a fibric‐acid deriv­ative 1,9 . Small‐framed, older patients with renal impairment are particularly prone to combination statin and fibrate‐induced myopathy 10 .…”