BEZAFIBRATE - AN UPDATE OF ITS PHARMACOLOGY AND USE IN THE MANAGEMENTOF DYSLIPIDEMIA

The lipid-modifying profile of bezafibrate is characterised by marked decreases in elevated triglyceride levels, increases in high density l ipoprotein (HDL) cholesterol levels and decreases in total and low den sity lipoprotein (LDL) cholesterol levels. Bezafibrate also reduces el evated levels of lipoprotein(a) [Lp(a)] and fibrinogen, which are inde pendent cardiovascular risk factors. Bezafibrate is effective in most types of primary and secondary dyslipidaemia. It is of greatest benefi t in conditions featuring hypertriglyceridaemia and/or HDL cholesterol deficiency. This is particularly true for patients with diabetes mell itus, notably those with non-insulin-dependent diabetes mellitus (NIDD M) who are also likely to have increased fibrinogen levels. In the lim ited comparisons available, there appear to be few consistent differen ces in lipid-modifying effects between bezafibrate and other fibrates. Compared with HMG-CoA reductase inhibitors, bezafibrate causes larger changes in triglyceride and, in general, HDL cholesterol levels, and has a lesser influence on LDL and total cholesterol levels. These diff erences are advantages when bezafibrate and HMG-CoA reductase inhibito rs are used as combined therapy in patients with severe dyslipidaemia unresponsive to either modality alone. The combination of bezafibrate plus an HMG-CoA reductase inhibitor in clinical trials has not led to the predicted increase in myalgia. Indeed, bezafibrate is generally fr ee of serious unwanted effects: rhabdomyolysis is rare and has occurre d mainly in patients with renal dysfunction given excessive dosages. O ther patient groups in whom bezafibrate has improved serum lipid profi les are those with isolated HDL cholesterol deficiency, dyslipidaemia secondary to renal insufficiency, and following cardiac surgery or oth er procedures. However, data for these indications are not extensive. Evidence is now available to show a beneficial effect of bezafibrate o n retarding atherosclerotic processes and in reducing risk of coronary heart disease. The 5-year Bezafibrate Coronary Atherosclerosis Interv ention Trial (BECAIT) in young male survivors of myocardial infarction demonstrated a smaller decrease in luminal diameter and a reduction i n coronary events with bezafibrate compared with placebo. The Bezafibr ate Infarction Prevention (BIP) study is expected to provide mortality data which is currently lacking for bezafibrate. In conclusion, bezaf ibrate is a useful and well-tolerated lipid-modifying agent in the man agement of primary with hypertriglyceridaemia and/or low HDL cholester ol levels, and reduces fibrinogen levels. Together with its ability to sustain or improve glycaemic control, these properties make it a logi cal choice for treating patients with diabetes mellitus and dyslipidae mia. Additionally, the drug may be of value as combination therapy in patients with severe dyslipidaemia. Importantly, there is evidence tha t the drug can slow the atherosclerotic process and reduce cardiovascu lar morbidity. The ongoing BIP secondary intervention study and other investigations will help clarify the effects of bezafibrate on cardiov ascular mortality and morbidity.