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

M. D. Feher, J. Foxton, D. Banks, A. F. Lant, R. Wray

Department of Clinical Pharmacology and Therapeutics, Charing Cross and Westminster Medical School, London.

OBJECTIVE--To evaluate the long-term safety profile of treatment with a statin-fibrate combination in a cohort of patients with documented coronary artery disease. DESIGN--Retrospective cohort analytical study. SETTING--District general hospital. PATIENTS--102 (81 male and 21 female) hypercholesterolaemic (total cholesterol concentration > 6.5 mmol/l) patients with documented coronary artery disease and who had been treated with a statin-fibrate combination for over 1 year. Coronary artery disease was confirmed by angiography in 93 patients and by a positive (Bruce protocol) exercise test in the remainder. Fifty eight patients had a history of previous coronary bypass graft surgery. 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) mmol/l 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 simvastatin-bezafibrate 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.

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