Abstract 18582: Correlation Between Reductions in LDL-cholesterol, Apolipoprotein B, and Lipoprotein(a) with Mipomersen in FH and Other Hypercholesterolemic Patients at High Risk for Coronary Disease

Abstract

Introduction: Familial hypercholesterolemia (FH) is characterized by markedly elevated LDL-cholesterol (LDL-c) and, if untreated, premature atherosclerosis. Current treatment modalities are directed toward lowering LDL-c, although other atherogenic lipoproteins such as lipoprotein(a) [Lp(a)] are also considered independent causal risk factors for CHD. Lp(a) levels are about 2-fold higher in FH patients. However the LDL receptor is probably not the major route of Lp(a) clearance as statin therapy does not lower Lp(a). As Apo B is an integral component of Lp(a), inhibiting Apo B would be expected to reduce Lp(a) levels.

Methods : We evaluated the relationship between the reduction in LDL-c, Apo B, and Lp(a) levels in patients with FH or hypercholesterolemia at high risk for CHD (N=256)and already receiving maximum tolerated lipid-lowering therapy, following treatment with mipomersen, an antisense Apo B synthesis inhibitor.

Results: Table shows the absolute and percent changes in lipoprotein parameters pre/post mipomersen 200mg SC weekly for 26 weeks.Percent reductions in LDL-c and Apo B pre/post treatment were tightly correlated (r =0.95, p<0.0001). There was also a positive, but moderate, linear correlation between the percent reductions in Apo B and Lp(a) pre/post treatment (r =0.43, p<0.0001 ).

Conclusion: Inhibiting Apo B synthesis with mipomersen reduced not only LDL-c and Apo B, but also Lp(a), and therefore represents a novel potential approach to reducing all three of these atherogenic lipid fractions. *LDL-c and Apo B results are in mean (SD) and Lp(a) in median (CI)