What drugs should I choose to treat dyslipidaemia, and how should I monitor treatment?

Statins inhibit the conversion of HMG-CoA to mevalonate (the rate-determining step in cholesterol synthesis). Hepatic LDL receptors (recognising both apoproteins E and B) are upregulated, and uptake of LDL cholesterol and remnant particles (IDL) is increased. Hepatic VLDL output is also modestly decreased. Plasma LDL-cholesterol levels thus fall by 30–60% with the bulk of the decrease with the starting dose. A further 7% LDL reduction is obtained for each doubling of the dose. HDL cholesterol levels are modestly reduced (
8%), and if plasma triglyceride levels are above 2.5mmol/l, these are lowered by a similar fraction as LDL.

Statins are the first choice for patients requiring LDL reduction, and for treatment of mixed lipaemia if triglycerides are below 5mmol/l. Action on hepatic VLDL output probably underlies the modest reduction in cholesterol levels in patients homozygous for receptor negative familial hypercholesterolaemia (FH). There is little information on the use of statins in children, and they should be stopped in women at least 6 weeks prior to conception.

Anion-exchange resins interrupt the enterohepatic circulation of bile and cholesterol, causing body levels to fall. Hepatic LDL activity is upregulated to obtain cholesterol for new bile acid formation. LDL reductions of up to 30% can be achieved. They may increase triglyceride levels to a modest and often transient degree. Their poor tolerability generally reserves them for use in children heterozygous for FH, the treatment (in combination with statins) of severe adult FH, in FH women contemplating pregnancy (when some physicians use them in preference to statins) and in patients intolerant of statins. The resins have been used with positive outcome in several angiographic trials and in an early positive end point trial (the Lipid Research Clinics trial).

Fibrates are ligands for the nuclear hormone receptors, peroxisome proliferation activator receptors (PPARs). They decrease apoprotein C-III synthesis (an inhibitor of lipoprotein lipase) and therefore increase lipoprotein lipase activity. Triglyceride levels thus fall by 40–60%. They also upregulate apoprotein A-1 synthesis (the major protein of HDL). HDL cholesterol levels rise by 10–20%. Fibrates also lower LDL cholesterol in primary hypercholesterolaemia (type IIa hyperlipidaemia) by 15–25%. They are first line treatment for severe hypertriglyceridaemia and (in combination with statins) in severe mixed lipaemia. They are second line drugs in patients intolerant of statins for hypercholesterolaemia and mixed lipaemia. Data from end point clinical trials are not extensive and concerns over fibrate safety have remained since the original WHO clofibrate trial which was associated with increased non-CHD deaths. However the Helsinki Heart Study showed a positive outcome and the recent VA HIT trial, again with gemfibrozil, was positive. However the recent secondary BIP prevention study with bezafibrate was negative.

High dose fish oil capsules have a role in the treatment of severe hypertriglyceridaemia. They reduce hepatic VLDL output. In practice they are used in combination with fibrates and occasionally statins. The author has also used them in rare patients with familial hypertriglyceridaemia during pregnancy to protect against pancreatitis.