GEMFIBROZIL - A REAPPRAISAL OF ITS PHARMACOLOGICAL PROPERTIES AND PLACE IN THE MANAGEMENT OF DYSLIPIDEMIA

Gemfibrozil improves lipid and apolipoprotein profiles, particularly v ery low density lipoprotein (VLDL) triglyceride and high density lipop rotein (HDL) cholesterol levels, in patients with dyslipidaemia when a dministered at a total daily dose of 900 or 1200mg. As demonstrated by the Helsinki Heals Study, these effects result in a reduction in some risk factors for coronary heart disease (CHD) and also a 34% reductio n in the incidence of this disease after 5 years compared with placebo . Limited data suggest that gemfibrozil has beneficial effects on the fibrinolytic system and may slow the progression of atherosclerosis. G emfibrozil has shown efficacy in the treatment of patients with type I Ia, IIb, III, IV or V dyslipidaemia or hypoalphalipoproteinaemia, espe cially in patients with elevated triglyceride and low HDL cholesterol levels. It is also effective in patients with non-insulin-dependent di abetes mellitus (NIDDM) and dyslipidaemia and has no detrimental effec ts on glycaemic control. A small number of studies also showed gemfibr ozil to be effective for the control of dyslipidaemia associated with renal failure, transplantation, nephrotic syndrome, arterial occlusive disease or systemic lupus erythematosus. However, patients with pre-e xisting CHD do not appear to derive the same benefits (reduced CHD mor tality) from gemfibrozil therapy as these other patients, although res ults are based on studies of limited size and number. In general gemfi brozil has at feast similar efficacy to bile acid sequestrants and oth er fibric acid derivatives. Comparisons with HMG-CoA reductase inhibit ors show these agents to produce different effects on lipid profiles f rom gemfibrozil. Thus, gemfibrozil would be expected to be superior in some patients (those with elevated triglyceride or VLDL cholesterol l evels), but HMG-CoA reductase inhibitors should have greater benefits in those with elevated low density lipoprotein cholesterol levels. Thu s, in patients with elevated triglyceride levels and low HDL cholester ol levels, and, particularly inpatients with NIDDM, gemfibrozil is a u seful treatment option, which has been shown to reduce the risk of CHD in middle aged men. However, limited available data prevents the accu rate comparison of this agent with HMG-CoA reductase inhibitors in pat ients with this lipid profile. Gemfibrozil is a nonhalogenated phenoxy pentanoic acid derivative which improves lipid and apolipoprotein prof iles in patients with dyslipidaemia. in particular, very low density l ipoprotein (VLDL) triglyceride and cholesterol levels are reduced and high density lipoprotein (HDL) cholesterol levels are increased. Altho ugh gemfibrozil reduces HMG-CoA reductase activity in human mononuclea r cells, it appears to act predominantly by increasing lipoprotein lip ase activity. It also increases levels of apolipoprotein A-I mRNA tran scripts and decreases those of apolipoprotein B mRNA. Although evidenc e is equivocal, it appears that gemfibrozil increases fibrinolysis. Fi brinogen levels are often decreased after gemfibrozil therapy, althoug h a number of studies have shown these levels to increase. Similarly, plasminogen size and distribution [gemfibrozil has a beneficial effect on small dense LDL particles (section 1,1)]. However, further clinica l study of this therapy, principally its tolerability profile, is requ ired. Thus, gemfibrozil is an effective agent for the treatment of pat ients with dyslipidaemia, particularly those with elevated triglycerid e levels and low HDL cholesterol levels, a pattern of dyslipidaemia ty pical of those with NIDDM and common in patients with CHD. Notably, it reduces the risk of CHD in middle aged men. However, insufficient dir ect comparisons are available to accurately place this agent in relati on to alternative lipid lowering agents, including HMG-CoA reductase i nhibitors and other fibric acid derivatives, in patients with this lip id profile.