Mipomersen, an Apolipoprotein B Synthesis Inhibitor, Reduces Atherogenic Lipoproteins in Patients With Severe Hypercholesterolemia at High Cardiovascular Risk
Open accessAbstract
Objectives This study sought to examine the efficacy and safety of mipomersen for reducing atherogenic lipids and lipoproteins in patients with hypercholesterolemia. Background Many patients on lipid-lowering therapies remain unable to achieve target low-density lipoprotein (LDL) cholesterol levels. Mipomersen, an antisense oligonucleotide inhibitor of apolipoprotein B, reduces LDL cholesterol and atherogenic lipoproteins. Methods This randomized, double-blind, multicenter study enrolled 158 patients with baseline LDL cholesterol levels ≥100 mg/dl with, or at high risk for, coronary heart disease who were receiving maximally tolerated lipid-lowering therapy. Patients received weekly subcutaneous mipomersen 200 mg (n = 105) or placebo (n = 52) for 26 weeks, with a 24-week follow-up period. Randomization was stratified by type 2 diabetes status. Results Sixty mipomersen and 44 placebo patients completed treatment. Mean baseline LDL cholesterol levels were 122.7 and 122.6 mg/dl in the placebo and mipomersen patients, respectively. Mipomersen reduced LDL cholesterol by -36.9% compared with placebo at -4.5% (p < 0.001). Target LDL cholesterol <100 mg/dl was attained in 76% of mipomersen and 38% of placebo patients. Mipomersen also significantly reduced apolipoprotein B (-38%) and lipoprotein(a) (-24%) (p < 0.001). Common adverse events included injection site reactions (78% with mipomersen, 31% with placebo) and flu-like symptoms (34% with mipomersen, 21% with placebo). Elevations in transaminases and liver fat also occurred in some patients, and these levels returned toward baseline after treatment cessation. Conclusions Mipomersen significantly reduced LDL cholesterol, apolipoprotein B, and lipoprotein(a) in patients with hypercholesterolemia with, or at risk for, coronary heart disease not controlled by existing therapies. (Safety and Efficacy of Mipomersen [ISIS 301012] as Add-On Therapy in High Risk Hypercholesterolemic Patients; NCT00770146).
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ASOs targeting ApoB mRNA, such as mipomersen, can reduce both LDL cholesterol and Lp(a) levels, but their side effects limit their use.
“ASOs targeting ApoB mRNA, such as mipomersen, can reduce both LDL cholesterol and Lp(a) levels, but their side effects limit their use [16].”
From Residual Cardiovascular Risk: Role of Remnants Cholesterol, Monocyte/HDL Ratio and Lipoprotein Ratios on Personalized Cardiovascular Prevention (2024) · cites this paper as [16]
Cites
Grundy, S. M., Cleeman, J. I., Merz, C. N. B., Brewer, H. B., Clark, L. T., Hunninghake, D. B., Pasternak, R. C., Smith, S. C., & Stone, N. J. (2004) · Circulation · doi:10.1161/01.cir.0000133317.49796.0e · Cited by 6,902 · see citing works
Transfer of low density lipoprotein into the arterial wall and risk of atherosclerosis
Nielsen, L. B. (1996) · Atherosclerosis · doi:10.1016/0021-9150(96)05802-9 · Cited by 186 · see citing works
McKenney, J. M., Jones, P. H., Bays, H. E., Knopp, R. H., Kashyap, M. L., Ruoff, G. E., & McGovern, M. E. (2007) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2006.11.037 · Cited by 150 · see citing works
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Very Low Levels of Atherogenic Lipoproteins and the Risk for Cardiovascular Events
Boekholdt, S. M., Hovingh, G. K., Mora, S., Arsenault, B. J., Amarenco, P., Pedersen, T. R., LaRosa, J. C., Waters, D. D., DeMicco, D. A., Simes, R. J., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.02.615 · Cited by 581 · see citing works
Resistance and intolerance to statins
Reiner, Ž. (2014) · Nutrition, Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2014.05.009 · Cited by 225 · see citing works
From Lipids to Inflammation: New Approaches to Reducing Atherosclerotic Risk
Shapiro, M. D., & Fazio, S. (2016) · Circulation Research · doi:10.1161/circresaha.115.306471 · Cited by 217 · see citing works
Lipid-Lowering Agents: Targets Beyond PCSK9
Hegele, R. A., & Tsimikas, S. (2019) · Circulation Research · doi:10.1161/circresaha.118.313171 · Cited by 171 · see citing works
Fogacci, F., Ferri, N., Toth, P. P., Ruscica, M., Corsini, A., & Cicero, A. F. G. (2019) · Drugs · doi:10.1007/s40265-019-01114-z · Cited by 132 · see citing works
Postprandial lipemia as a cardiometabolic risk factor
Pirillo, A., Norata, G. D., & Catapano, A. L. (2014) · Current Medical Research and Opinion · doi:10.1185/03007995.2014.909394 · Cited by 108 · see citing works
Mipomersen and its use in familial hypercholesterolemia
Parham, J. S., & Goldberg, A. C. (2019) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2018.1550071 · Cited by 94 · see citing works
Unmet Needs in LDL-C Lowering: When Statins Won’t Do!
Krähenbühl, S., Pavik-Mezzour, I., & von Eckardstein, A. (2016) · Drugs · doi:10.1007/s40265-016-0613-0 · Cited by 89 · see citing works
Stahel, P., Xiao, C., Hegele, R. A., & Lewis, G. F. (2018) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2017.12.007 · Cited by 75 · see citing works
Li, N., Li, Q., Tian, X.-Q., Qian, H.-Y., & Yang, Y.-J. (2014) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-014-0077-0 · Cited by 45 · see citing works
Injection site reactions after subcutaneous oligonucleotide therapy
van Meer, L., Moerland, M., Gallagher, J., van Doorn, M. B. A., Prens, E. P., Cohen, A. F., Rissmann, R., & Burggraaf, J. (2016) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12961 · Cited by 45 · see citing works
Safety and tolerability of injectable lipid-lowering drugs: a review of available clinical data
Cicero, A. F., Tartagni, E., & Ertek, S. (2014) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2014.932348 · Cited by 39 · see citing works
Agarwala, A., Jones, P., & Nambi, V. (2015) · Current Atherosclerosis Reports · doi:10.1007/s11883-014-0467-4 · Cited by 31 · see citing works
Treatment of children with homozygous familial hypercholesterolaemia
Reiner, Ž. (2018) · European Journal of Preventive Cardiology · doi:10.1177/2047487318781360 · Cited by 18 · see citing works
Sucato, V., Comparato, F., Ortello, A., Galassi, A. R., & Novo, G. (2024) · Journal of Personalized Medicine · doi:10.3390/jpm14050460 · Cited by 12 · see citing works
“ASOs targeting ApoB mRNA, such as mipom-ersen, can reduce both LDL cholesterol and Lp(a) levels, but their side effects limit their use [16].”
Background
- Authors
- Thomas, G. S., Cromwell, W. C., Ali, S., Chin, W., Flaim, J. D., & Davidson, M.
- Affiliations
- University of California, Irvine (US)
- Ionis Pharmaceuticals (United States) (US)
- University of Chicago (US)
- Corresponding author
- Thomas, Gregory S.
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 62
- Issue
- 23
- Pages
- 2178-2184
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W54812721
- Cited by
- 245
- References
- 3
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 12 · 2023: 10 · 2022: 21 · 2021: 15 · 2020: 10 · 2019: 24 · 2018: 10 · 2017: 11 · 2016: 30 · 2015: 39 · 2014: 38 · 2013: 3 · 2012: 1
- FWCI
- 36.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Isis Pharmaceuticals and Genzyme Corporation
- Genzyme, Regeneron, and sanofi-aventis
- Isis Pharmaceuticals
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- mipomersen, apolipoprotein B, antisense oligonucleotides, severe hypercholesterolemia, LDL cholesterol lowering, lipoprotein(a), atherogenic lipoproteins, coronary heart disease risk, adjunctive therapy, type 2 diabetes, injection site reactions, transaminase elevation, liver fat, drug safety and efficacy
- MeSH terms
- Adult, Aged, Anticholesteremic Agents, Apolipoproteins B, Cardiovascular Diseases, Double-Blind Method, Drug Administration Schedule, Female, Humans, Hypercholesterolemia, Hyperlipoproteinemia Type II, Cholesterol, LDL, Male, Middle Aged, Oligonucleotides, Risk Factors, Treatment Outcome, Risk Assessment, Atherosclerosis
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