A 6-month randomised study of the combination of fenofibrate and simvastatin in patients with mixed dyslipidaemia at risk of cardiovascular disease not adequately controlled by simvastatin 40mg alone

Abstract

Purpose: Guidelines recognise the potential of fibrates in combination with statins in patients with mixed dyslipidaemia and coronary heart disease (CHD) or CHD risk equivalence. In this setting, the effect of fenofibrate in patients whose lipid levels were not adequately controlled by simvastatin alone was tested in a double-blind, randomised study. Methods: Non-diabetic subjects with CHD or CHD risk equivalent or multiple risk factors, mixed dyslipidaemia and not at lipid goals after 6-week of simvastatin 40 mg run-in were randomly assigned to either 145 mg fenofibrate + 40 mg simvastatin (F+S) or 145 mg fenofibrate placebo + 40 mg simvastatin (S) for 24 weeks (W). The objectives were to demonstrate superiority of (F+S) over (S) for percent change in TG, HDL-C and LDL-C after 12 weeks and for percent change in lipids, non-HDL-C and apoB:apoA1 ratio after 24 weeks. Results: At 12 weeks, (F+S) was superior to (S) in reducing TG, -28.2%, and increasing HDL-C, +6.5% (both p<0.001). LDL-C decrease was similar in (F+S) and (S), -7.7% vs -6.5% respectively. At 24 weeks (F+S) was superior to (S) on all lipid parameters including LDL-C (see table). Treatments with (F+S) and (S) were equally well tolerated. Adding fenofibrate 145 mg to simvastatin 40 mg did not increase the incidence of increased liver enzymes or musculoskeletal symptoms (no case of rhabdomyolysis). [...]