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Waldmann, Elisa; Vogt, Anja; Crispin, Alexander; Altenhofer, Julia; Riks, Ina; Parhofer, Klaus G. (2017): Effect of mipomersen on LDL-cholesterol in patients with severe LDL-hypercholesterolaemia and atherosclerosis treated by lipoprotein apheresis (The MICA-Study). In: Atherosclerosis, Vol. 259: pp. 20-25
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BACKGROUND AND AIMS In this study, we evaluated the effect of mipomersen in patients with severe LDL-hypercholesterolaemia and atherosclerosis, treated by lipid lowering drugs and regular lipoprotein apheresis. METHODS This prospective, randomized, controlled phase II single center trial enrolled 15 patients (9 males, 6 females; 59~±~9 y, BMI 27~±~4~kg/m(2)) with established atherosclerosis, LDL-cholesterol \geq130~mg/dL (3.4~mmol/L) despite maximal possible drug therapy, and fulfilling German criteria for regular lipoprotein apheresis. All patients were on stable lipid lowering drug therapy and regular apheresis for \textgreater3 months. Patients randomized to treatment (n~=~11) self-injected mipomersen 200~mg sc weekly, at day 4 after apheresis, for 26 weeks. Patients randomized to control (n~=~4) continued apheresis without injection. The primary endpoint was the change in pre-apheresis LDL-cholesterol. RESULTS Of the patients randomized to mipomersen, 3 discontinued the drug early (\textless12 weeks therapy) for side effects. For these, another 3 were recruited and randomized. Further, 4 patients discontinued mipomersen between 12 and 26 weeks for side effects (moderate to severe injection site reactions n~=~3 and elevated liver enzymes n~=~1). In those treated for \textgreater12 weeks, mipomersen reduced pre-apheresis LDL-cholesterol significantly by 22.6~±~17.0%, from a baseline of 4.8~±~1.2~mmol/L to 3.7~±~0.9~mmol/L, while there was no significant change in the control group (+1.6~±~9.3%), with the difference between the groups being significant (p=0.02). Mipomersen also decreased pre-apheresis lipoprotein(a) (Lp(a)) concentration from a median baseline of 40.2~mg/dL (32.5,71) by 16% (-19.4,13.6), though without significance (p=0.21). CONCLUSIONS Mipomersen reduces LDL-cholesterol (significantly) and Lp(a) (non-significantly) in patients on maximal lipid-lowering drug therapy and regular apheresis, but is often associated with side effects.