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.


METHODS
Retrospective cohort analytical study.


METHODS
District general hospital.


METHODS
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.


METHODS
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.


METHODS
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.
Feher
M D
MD
Department of Clinical Pharmacology and Therapeutics, Charing Cross and Westminster Medical School, London.
Foxton
J
J
Banks
D
D
Lant
A F
AF
Wray
R
R
D000328:Adult; D000368:Aged; D001219:Aspartate Aminotransferases / Q000097:blood; D001629:Bezafibrate / Q000009:adverse effects; D015331:Cohort Studies; D003327:Coronary Disease / Q000517:prevention & control*; D003402:Creatine Kinase / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D011345:Fenofibrate / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008148:Lovastatin / Q000009:adverse effects / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000009:adverse effects; D012189:Retrospective Studies; D019821:Simvastatin
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008148:Lovastatin; D019821:Simvastatin; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase; D017035:Pravastatin; D011345:Fenofibrate; D001629:Bezafibrate