Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy
| dc.contributor.author | McGowan, M. P. | en_ZA |
| dc.contributor.author | Tardif, J. C. | en_ZA |
| dc.contributor.author | Ceska, R. | en_ZA |
| dc.contributor.author | Burgess, L. J. | en_ZA |
| dc.contributor.author | Soran, H. | en_ZA |
| dc.contributor.author | Gouni-Berthold, I. | en_ZA |
| dc.contributor.author | Wagener, G. | en_ZA |
| dc.contributor.author | Chasan-Taber, S. | en_ZA |
| dc.date.accessioned | 2013-02-23T09:31:11Z | |
| dc.date.available | 2013-02-23T09:31:11Z | |
| dc.date.issued | 2012-11-13 | |
| dc.description | The original publication available at www.plos.org | en_ZA |
| dc.description | CITATION: McGowan, M. P. et al. 2012. Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy. PLoS ONE, 7(11):e49006, doi:10.1371/journal.pone.0049006. | |
| dc.description.abstract | Objectives: Mipomersen, an antisense oligonucleotide targeting apolipoprotein B synthesis, significantly reduces LDL-C and other atherogenic lipoproteins in familial hypercholesterolemia when added to ongoing maximally tolerated lipid-lowering therapy. Safety and efficacy of mipomersen in patients with severe hypercholesterolemia was evaluated. Methods and Results: Randomized, double-blind, placebo-controlled, multicenter trial. Patients (n = 58) were $18 years with LDL-C $7.8 mmol/L or LDL-C $5.1 mmol/L plus CHD disease, on maximally tolerated lipid-lowering therapy that excluded apheresis. Weekly subcutaneous injections of mipomersen 200 mg (n = 39) or placebo (n = 19) were added to lipid-lowering therapy for 26 weeks. Main outcome: percent reduction in LDL-C from baseline to 2 weeks after the last dose of treatment. Mipomersen (n = 27) reduced LDL-C by 36%, from a baseline of 7.2 mmol/L, for a mean absolute reduction of 2.6 mmol/L. Conversely, mean LDL-C increased 13% in placebo (n = 18) from a baseline of 6.5 mmol/L (mipomersen vs placebo p,0.001). Mipomersen produced statistically significant (p,0.001) reductions in apolipoprotein B and lipoprotein(a), with no change in high-density lipoprotein cholesterol. Mild-to-moderate injection site reactions were the most frequently reported adverse events with mipomersen. Mild-to-moderate flu-like symptoms were reported more often with mipomersen. Alanine transaminase increase, aspartate transaminase increase, and hepatic steatosis occurred in 21%, 13% and 13% of mipomersen treated patients, respectively. Adverse events by category for the placebo and mipomersen groups respectively were: total adverse events, 16(84.2%), 39(100%); serious adverse events, 0(0%), 6(15.4%); discontinuations due to adverse events, 1(5.3%), 8(20.5%) and cardiac adverse events, 1(5.3%), 5(12.8%). Conclusion: Mipomersen significantly reduced LDL-C, apolipoprotein B, total cholesterol and non-HDL-cholesterol, and lipoprotein(a). Mounting evidence suggests it may be a potential pharmacologic option for lowering LDL-C in patients with severe hypercholesterolemia not adequately controlled using existing therapies. Future studies will explore alternative dosing schedules aimed at minimizing side effects. | en_ZA |
| dc.description.uri | http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0049006 | |
| dc.description.version | Publisher's version | en_ZA |
| dc.format.extent | 10 pages | |
| dc.identifier.citation | McGowan, M. P. et al. 2012. Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy. PLoS ONE, 7(11):e49006, doi:10.1371/journal.pone.0049006. | en_ZA |
| dc.identifier.issn | 1932-6203 (online) | |
| dc.identifier.other | 10.1371/journal.pone.0049006 | |
| dc.identifier.uri | http://hdl.handle.net/10019.1/79601 | |
| dc.language.iso | en_ZA | en_ZA |
| dc.publisher | PLoS | en_ZA |
| dc.rights.holder | Authors retain copyright | |
| dc.subject | Oligonucleotide | en_ZA |
| dc.subject | Apolipoprotein B | en_ZA |
| dc.subject | Low density lipoproteins | en_ZA |
| dc.subject | atherogenic lipoproteins | en_ZA |
| dc.subject | Hypercholesterolemia | en_ZA |
| dc.subject | Antilipemic agents | en_ZA |
| dc.subject | Mipomersen | en_ZA |
| dc.title | Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy | en_ZA |
| dc.type | Article | en_ZA |