|Derfler K, Goldammer A|
Combined LDL-Apheresis and Statin Treatment in Homozygous and Heterozygous Familial Hyperlipoproteinaemia
Journal of Clinical and Basic Cardiology 2001; 4 (2): 139-144
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Keywords: Atorvastatin, familiäre Hypercholesterinämie, fibrinogen, LDL-Apherese, Atorvastatin, familial hypercholesterolaemia, fibrinogen, LDL-apheresis
Familial hypercholesterolaemia (FH) is due to an autosomal dominantly inherited deficiency of LDL-receptor expression on the cell surface, leading to excess concentrations of serum total- and LDL-cholesterol followed by severe premature atherosclerosis. In patients with heterozygous FH it has been demonstrated that despite statin therapy (80 mg of atorvastatin), LDL-apheresis could significantly stimulate the residual LDL-receptor expression via the reduction of available extracellular cholesterol resulting in delayed reappearance of hypercholesterolaemia in between treatments (J. Streicher et al. J Investig Med 1999; 47: 378-87). The presented results of a cross-over evaluation in FH patients maintained on LDL-apheresis received initially 40 mg of simvastatin, followed by a wash-out period of four weeks and thereafter atorvastatin at a dosage of 10 mg to 80 mg. LDL-cholesterol levels obtained before apheresis treatment were further lowered by 26 % when patients were changed in medication from simvastatin (40 mg) to atorvastatin (80 mg; p < 0.05). When LDL-cholesterol concentrations were determined on 80 mg of atorvastatin and compared to the values at the end of the wash-out period a reduction of 39 % (p < 0.005) in LDL-cholesterol levels before LDL-apheresis treatment was observed. Subsequent to therapeutic LDL-apheresis treatment the LDL-cholesterol levels increased in a first order kinetic to a range of LDL-cholesterol at day 7 (the day of the next treatment) almost equal to the pretreatment values observed at the beginning of the kinetic study. Statin-therapy however, was able to delay the occurrence of LDL-cholesterol significantly resulting in a continuous decrease in LDL-cholesterol pretreatment values (LDL-chol: without/with statin therapy: 257 ± 32 mg/dl; 156 ± 29 mg/dl, p < 0.005). No side effects had to be observed during simvastatin and atorvastatin therapy at escalating dosage. Fibrinogen concentrations remained almost unchanged for the entire study period the values obtained being within the normal range in general. From these results we conclude that statin treatment is recommended in patients maintained long-term on LDL-apheresis to improve the lipoprotein pattern in homozygous and serious heterozygous FH. With these treatment options delayed progression or even regression of cardiovascular and vascular disease has been observed.