The Effect of Mipomersen in the Management of Patients with Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis of Clinical Trials
<b>Background:</b> Familial hypercholesterolemia (FH) lead to significant adverse effects in coronary arteries. Mipomersen is a second-generation antisense oligonucleotide that inhibits the synthesis of apolipoprotein B-100, an essential component of low density lipoprotein (LDL), and th...
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doaj-6e717237eb6e428499724031a43f22472021-07-23T13:47:42ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252021-07-018828210.3390/jcdd8070082The Effect of Mipomersen in the Management of Patients with Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis of Clinical TrialsBehrooz Astaneh0Nima Makhdami1Vala Astaneh2Gordon Guyatt3Department of Health Research Methods, Evidence & Impact (HEI), McMaster University, Hamilton, ON L8S 4K1, CanadaResearch Institute, St. Josef’s Healthcare, Hamilton, ON L8N 4A6, CanadaFaculty of Kinesiology and Health Sciences, York University, Toronto, ON M3J 1P3, CanadaDepartment of Health Research Methods, Evidence & Impact (HEI), McMaster University, Hamilton, ON L8S 4K1, Canada<b>Background:</b> Familial hypercholesterolemia (FH) lead to significant adverse effects in coronary arteries. Mipomersen is a second-generation antisense oligonucleotide that inhibits the synthesis of apolipoprotein B-100, an essential component of low density lipoprotein (LDL), and thus decreases the production of LDL. We aimed to determine the effect of mipomersen in patients with FH. <b>Methods:</b> We searched Ovid Medline, Ovid EMBASE, WHO ICTRP search portal, ISI database, the reference lists of relevant articles, and also Google Scholar to retrieve articles. All randomized controlled trials (RCTs) comparing patients with FH receiving mipomersen as an add-on and a parallel group receiving a placebo or no intervention were selected. <b>Results:</b> Five studies with more than 500 patients were included. All had low risk of bias. Pooling data showed that mipomersen probably reduces LDL compared with placebo [mean difference: −24.79, 95% CI (−30.15, −19.43)] but with a moderate level of certainty. There was a high level of evidence for injection site reactions [RR = 2.56, CI (1.47–4.44)] and a low level for increased serum alanine transaminase (ALT) > 3 times upper limit of normal (ULN) [RR = 5.19, CI (1.01–26.69)]. <b>Conclusion:</b> A moderate level of evidence in decreasing serum LDL indicates that we are uncertain if this drug provides benefit in any outcome important to patients. Although a low level of evidence for an increase in serum ALT leaves uncertainty about this adverse effect, injection site reactions in 10% or more of patients can be an important concern.https://www.mdpi.com/2308-3425/8/7/82familial hypercholesterolemiamipomersensystematic reviewmeta-analysislow-density lipoproteins |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Behrooz Astaneh Nima Makhdami Vala Astaneh Gordon Guyatt |
spellingShingle |
Behrooz Astaneh Nima Makhdami Vala Astaneh Gordon Guyatt The Effect of Mipomersen in the Management of Patients with Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis of Clinical Trials Journal of Cardiovascular Development and Disease familial hypercholesterolemia mipomersen systematic review meta-analysis low-density lipoproteins |
author_facet |
Behrooz Astaneh Nima Makhdami Vala Astaneh Gordon Guyatt |
author_sort |
Behrooz Astaneh |
title |
The Effect of Mipomersen in the Management of Patients with Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis of Clinical Trials |
title_short |
The Effect of Mipomersen in the Management of Patients with Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis of Clinical Trials |
title_full |
The Effect of Mipomersen in the Management of Patients with Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis of Clinical Trials |
title_fullStr |
The Effect of Mipomersen in the Management of Patients with Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis of Clinical Trials |
title_full_unstemmed |
The Effect of Mipomersen in the Management of Patients with Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis of Clinical Trials |
title_sort |
effect of mipomersen in the management of patients with familial hypercholesterolemia: a systematic review and meta-analysis of clinical trials |
publisher |
MDPI AG |
series |
Journal of Cardiovascular Development and Disease |
issn |
2308-3425 |
publishDate |
2021-07-01 |
description |
<b>Background:</b> Familial hypercholesterolemia (FH) lead to significant adverse effects in coronary arteries. Mipomersen is a second-generation antisense oligonucleotide that inhibits the synthesis of apolipoprotein B-100, an essential component of low density lipoprotein (LDL), and thus decreases the production of LDL. We aimed to determine the effect of mipomersen in patients with FH. <b>Methods:</b> We searched Ovid Medline, Ovid EMBASE, WHO ICTRP search portal, ISI database, the reference lists of relevant articles, and also Google Scholar to retrieve articles. All randomized controlled trials (RCTs) comparing patients with FH receiving mipomersen as an add-on and a parallel group receiving a placebo or no intervention were selected. <b>Results:</b> Five studies with more than 500 patients were included. All had low risk of bias. Pooling data showed that mipomersen probably reduces LDL compared with placebo [mean difference: −24.79, 95% CI (−30.15, −19.43)] but with a moderate level of certainty. There was a high level of evidence for injection site reactions [RR = 2.56, CI (1.47–4.44)] and a low level for increased serum alanine transaminase (ALT) > 3 times upper limit of normal (ULN) [RR = 5.19, CI (1.01–26.69)]. <b>Conclusion:</b> A moderate level of evidence in decreasing serum LDL indicates that we are uncertain if this drug provides benefit in any outcome important to patients. Although a low level of evidence for an increase in serum ALT leaves uncertainty about this adverse effect, injection site reactions in 10% or more of patients can be an important concern. |
topic |
familial hypercholesterolemia mipomersen systematic review meta-analysis low-density lipoproteins |
url |
https://www.mdpi.com/2308-3425/8/7/82 |
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