Astaneh Behrooz, Makhdami Nima, Astaneh Vala, Guyatt Gordon
Department of Health Research Methods, Evidence & Impact (HEI), McMaster University, Hamilton, ON L8S 4K1, Canada.
Research Institute, St. Josef's Healthcare, Hamilton, ON L8N 4A6, Canada.
J Cardiovasc Dev Dis. 2021 Jul 20;8(7):82. doi: 10.3390/jcdd8070082.
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. 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. 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)]. 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.
家族性高胆固醇血症（FH）会对冠状动脉产生严重不良影响。米泊美生是一种第二代反义寡核苷酸，可抑制载脂蛋白B-100（低密度脂蛋白（LDL）的一种重要成分）的合成，从而减少LDL的产生。我们旨在确定米泊美生对FH患者的影响。我们检索了Ovid Medline、Ovid EMBASE、世界卫生组织国际临床试验注册平台（WHO ICTRP）搜索门户、ISI数据库、相关文章的参考文献列表，还检索了谷歌学术以获取文章。我们纳入了所有比较接受米泊美生附加治疗的FH患者与接受安慰剂或无干预的平行组患者的随机对照试验（RCT）。纳入了五项涉及500多名患者的研究。所有研究的偏倚风险均较低。汇总数据显示，与安慰剂相比，米泊美生可能会降低LDL[平均差异：-24.79，95%置信区间（-30.15，-19.43）]，但确定性水平中等。注射部位反应有高水平证据[相对危险度（RR）=2.56，置信区间（1.47 - 4.44）]，血清丙氨酸转氨酶（ALT）升高超过正常上限（ULN）3倍有低水平证据[RR = 5.19，置信区间（1.01 - 26.69）]。血清LDL降低的证据水平中等，这表明我们不确定这种药物是否能为患者带来任何重要益处。虽然血清ALT升高的证据水平较低，使得这种不良反应存在不确定性，但10%或更多患者出现的注射部位反应可能是一个重要问题。
