FAMILIAL HYPERCHOLESTEROLEMIA REGRESSION STUDY - A RANDOMIZED TRIAL OF LOW-DENSITY-LIPOPROTEIN APHERESIS

Low-density-lipoprotein (LDL) apheresis has the theoretical advantage over anion-exchange resins and hydroxymethylglutaryl coenzyme A inhibi tors of decreasing lipoprotein(a) as well as LDL. To confirm this adva ntage, patients with heterozygous familial hypercholesterolaemia and c oronary artery disease were randomised to receive LDL apheresis fortni ghtly (with disposable dextran sulphate/cellulose columns) plus simvas tatin 40 mg daily, or colestipol 20 g plus simvastatin 40 mg daily. Qu antitative coronary angiography was repeated after a mean of 2.1 years in 20 patients undergoing apheresis and in 19 on combination drug the rapy. Changes in serum lipoproteins were similar in both groups apart from greater lowering by apheresis of LDL cholesterol (3.2 vs 3.4 mmol /L in drug group, p=0.03) and lipoprotein(a) (geometric means 14 vs 21 mg/dL, p=0.03). There were no significant differences in primary angi ographic endpoints per patient but lesion-based and segment-based seco ndary endpoints were biased in favour of the drug group (change in min imum lumen diameter of lesions 0.07 vs -0.004 mm, p=0.046; change in m ean lumen diameter of segments 0.02 vs -0.06 mm, p=0.01). None of the angiographic changes correlated with lipoprotein(a) concentrations. Pe r patient changes in % diameter stenosis and minimum lumen diameter in the two groups were as or more favourable than those observed in five published trials that assessed lipid-lowering drug therapy by quantit ative coronary angiography. Although LDL apheresis combined with simva statin was more effective than colestipol plus simvastatin in reducing LDL cholesterol and lipoprotein(a), it was less beneficial in influen cing coronary atherosclerosis and should be reserved for patients unre sponsive to drugs. Decreasing lipoprotein(a) seems to be unnecessary i f LDL cholesterol is reduced to 3.4 mmol/L or less.