Elisa Waldmann1, Anja Vogt2, Alexander Crispin3, Julia Altenhofer4, Ina Riks4, Klaus G Parhofer4. 1. Medizinische Klinik II, LMU, Klinikum der Universität München, Campus Großhadern, Germany. Electronic address: elisa.waldmann@med.uni-muenchen.de. 2. Medizinische Klinik IV, LMU, Klinikum der Universität München, Campus Innenstadt, Germany. 3. Department of Medical Informatics, Biometry, and Epidemiology, Ludwig Maximilians University Munich, Munich, Germany. 4. Medizinische Klinik II, LMU, Klinikum der Universität München, Campus Großhadern, Germany.
Abstract
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/m2) with established atherosclerosis, LDL-cholesterol≥130 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 >3 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 (<12 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 >12 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=0.006). Mipomersen also decreased pre-apheresis lipoprotein(a) (Lp(a)) concentration from a median baseline of 40.2mg/dL (32.5,71) by 15% (-19.4,3.6) though without significance (p=0.3). 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.
RCT Entities:
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/m2) with established atherosclerosis, LDL-cholesterol ≥130 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 >3 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 (<12 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 >12 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=0.006). Mipomersen also decreased pre-apheresis lipoprotein(a) (Lp(a)) concentration from a median baseline of 40.2mg/dL (32.5,71) by 15% (-19.4,3.6) though without significance (p=0.3). 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.
Authors: Jenny Sandmark; Anna Tigerström; Tomas Akerud; Magnus Althage; Thomas Antonsson; Stefan Blaho; Cristian Bodin; Jonas Boström; Yantao Chen; Anders Dahlén; Per-Olof Eriksson; Emma Evertsson; Tomas Fex; Ola Fjellström; David Gustafsson; Margareta Herslöf; Ryan Hicks; Emelie Jarkvist; Carina Johansson; Inge Kalies; Birgitta Karlsson Svalstedt; Fredrik Kartberg; Anne Legnehed; Sofia Martinsson; Andreas Moberg; Marianne Ridderström; Birgitta Rosengren; Alan Sabirsh; Anders Thelin; Johanna Vinblad; Annika U Wellner; Bingze Xu; Ann-Margret Östlund-Lindqvist; Wolfgang Knecht Journal: J Biol Chem Date: 2020-03-04 Impact factor: 5.157
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