New once-daily fibrate/statin combination

Prescribers now have the option to prescribe fenofibrate and simvastatin together in a single tablet for patients with mixed dyslipidaemia.

Response to fenofibrate/simvastatin therapy should be monitored by determination of serum cholesterol (shown here in crystal form) and triglycerides. | SCIENCE PHOTO LIBRARY
Response to fenofibrate/simvastatin therapy should be monitored by determination of serum cholesterol (shown here in crystal form) and triglycerides. | SCIENCE PHOTO LIBRARY

Further information
View Cholib drug record
Summaries of Product Characteristics
Manufacturer: BGP Products 
MIMS Cardiology Clinic

Cholib (fenofibrate/simvastatin) is available in two strengths each containing 145mg fenofibrate and 20mg or 40mg simvastatin. It is indicated as an adjunct to diet and exercise in adults with high cardiovascular risk and mixed dyslipidaemia, to reduce triglycerides and increase HDL-C levels when LDL-C levels are adequately controlled with the corresponding dose of simvastatin monotherapy.

Pharmacology of fenofibrate and simvastatin

Fenofibrate and simvastatin have different and complementary modes of action. Fenofibrate exerts its effects through activation of peroxisome proliferator activated receptor type alpha (PPARα) and has been shown to increase HDL-C levels while reducing LDL-C and VLDL-C levels. Simvastatin inhibits HMG-CoA reductase, an enzyme involved in cholesterol formation, and has been shown to reduce both normal and raised LDL-C levels as well as lowering levels of apolipoprotein B and plasma triglycerides and increasing levels of HDL-C.

Efficacy of fenofibrate/simvastatin combination

The safety and efficacy of fenofibrate/simvastatin were evaluated in four clinical studies involving 7583 patients with mixed dyslipidaemia, all of which began with a six-week statin run-in period followed by a 24-week double-blind treatment period.

Study 0502 compared a constant dose of fenofibrate/simvastatin (145mg/40mg) with simvastatin 40mg. At 24 weeks, the combination showed superiority over statin monotherapy for triglyceride reduction and HDL-C increase. The combination was associated with a non-significant additional 1.2% reduction in LDL-C at 12 weeks compared with monotherapy (p=0.539), which increased to a significant 7.2% reduction at 24 weeks (p=0.005). At 24 weeks the combination was superior to monotherapy with respect to all parameters except ApoA1 increase.

Another study (0501) compared two different doses of fenofibrate/simvastatin (145mg/20mg [baseline to 12 weeks] and 145mg/40mg [12 to 24 weeks]) with simvastatin 40mg. After 12 weeks fenofibrate/simvastatin 145mg/20mg was superior to monotherapy for triglyceride reduction (mean percent change from baseline -28.20 vs -4.60) and HDL-C (mean percent change from baseline, 7.32 vs 1.64) (p<0.001 for both) but did not meet the criteria for non-inferiority on LDL-C.

Supportive study in diabetes patients

The ACCORD (Action to Control Cardiovascular Risk in Diabetes) study (n=5518) was designed to evaluate the effect of a fenofibrate/simvastatin combination versus simvastatin monotherapy on non-fatal myocardial infarction, non-fatal stroke or death from cardiovascular causes (composite primary outcome) in patients with type II diabetes.

No significant differences in the composite primary outcome were observed for combination therapy versus monotherapy (hazard ratio [HR] 0.92 [95% CI 0.79-1.08], p=0.32). However, in the pre-specified subgroup of dyslipidaemic patients (HDL-C ≤0.88 mmol/L, triglyceride ≥2.3 mmol/L at baseline) the combination was associated with a 31% relative reduction (absolute risk reduction 4.95%) compared with monotherapy for the composite primary outcome (HR 0.69 [95% CI 0.49-0.97], p=0.03).

The researchers concluded that the findings do not support the use of fenofibrate/simvastatin combination therapy rather than statin monotherapy to reduce cardiovascular risk in the majority of patients with type II diabetes who are at high risk of cardiovascular disease. However, the findings suggest that the combination may benefit those patients with type II diabetes with substantial dyslipidaemia.

Safety of fenofibrate/simvastatin therapy

In clinical studies the adverse effects observed with fenofibrate/simvastatin combination therapy were in line with those reported for the individual components, the most commonly reported being upper respiratory tract infection, gastroenteritis and raised platelets, blood creatinine and alanine-aminotransferase.

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