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

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.