Exposure to alirocumab during the first trimester of pregnancy: A case report.
PCSK9 inhibitors
corpus callosum agenesis
familial hypercholesterolemia
pregnancy
Journal
Birth defects research
ISSN: 2472-1727
Titre abrégé: Birth Defects Res
Pays: United States
ID NLM: 101701004
Informations de publication
Date de publication:
01 09 2021
01 09 2021
Historique:
received:
31
05
2021
accepted:
02
06
2021
pubmed:
10
6
2021
medline:
3
11
2021
entrez:
9
6
2021
Statut:
ppublish
Résumé
Familial hypercholesterolemia can be efficiently treated with combined lipid-lowering drugs. Lipid-lowering drugs are usually withdrawn for pregnancy and breastfeeding, ideally preconception, followed by lipid apheresis, however, careful plans can be precipitated due to unexpected pregnancy. A 28-year old woman with familial hypercholesterolemia due to heterozygous LDLR mutations had an LDL-cholesterol level at 14.6 mmol/L and Lp(a) at 1150 mg/L. She required a three-vessel coronary artery bypass graft, drug-eluting stents, rosuvastatin, ezetimibe, and alirocumab at maximal dosage. Contraception was advised during the following 12 months, with a planned drug withdrawal to bridge with lipid apheresis, such as the direct adsorption of lipoproteins (DALI). However, an unplanned pregnancy required an abrupt stop of all oral medications at six gestational weeks, except for aspirin. Lipid apheresis controlled LDL-cholesterol in the range of 4.9-7.9 mmol/L (before DALI session) to 1.2-3.2 mmol/L (after DALI session). Later, the regular pregnancy ultrasounds highlighted an isolated agenesis of the corpus callosum later confirmed by magnetic resonance imaging. A causal link between the early pregnancy exposure to PCSK9 inhibitors (or statins and ezetimibe taken concomitantly) and the observed complete agenesis of the corpus callosum seems unlikely in this case. Guidelines do not specifically recommend preconception measures to lower fetal and/or maternal risks of patients with severe FH considering pregnancy. We argue that lipid apheresis and other measures should be discussed with women with FH and maternity project on an individual basis, until pharmacoepidemiology studies assessing the safety of PCSK9 inhibitors in pregnancy are available.
Sections du résumé
BACKGROUND
Familial hypercholesterolemia can be efficiently treated with combined lipid-lowering drugs. Lipid-lowering drugs are usually withdrawn for pregnancy and breastfeeding, ideally preconception, followed by lipid apheresis, however, careful plans can be precipitated due to unexpected pregnancy.
CASE
A 28-year old woman with familial hypercholesterolemia due to heterozygous LDLR mutations had an LDL-cholesterol level at 14.6 mmol/L and Lp(a) at 1150 mg/L. She required a three-vessel coronary artery bypass graft, drug-eluting stents, rosuvastatin, ezetimibe, and alirocumab at maximal dosage. Contraception was advised during the following 12 months, with a planned drug withdrawal to bridge with lipid apheresis, such as the direct adsorption of lipoproteins (DALI). However, an unplanned pregnancy required an abrupt stop of all oral medications at six gestational weeks, except for aspirin. Lipid apheresis controlled LDL-cholesterol in the range of 4.9-7.9 mmol/L (before DALI session) to 1.2-3.2 mmol/L (after DALI session). Later, the regular pregnancy ultrasounds highlighted an isolated agenesis of the corpus callosum later confirmed by magnetic resonance imaging.
CONCLUSIONS
A causal link between the early pregnancy exposure to PCSK9 inhibitors (or statins and ezetimibe taken concomitantly) and the observed complete agenesis of the corpus callosum seems unlikely in this case. Guidelines do not specifically recommend preconception measures to lower fetal and/or maternal risks of patients with severe FH considering pregnancy. We argue that lipid apheresis and other measures should be discussed with women with FH and maternity project on an individual basis, until pharmacoepidemiology studies assessing the safety of PCSK9 inhibitors in pregnancy are available.
Identifiants
pubmed: 34105316
doi: 10.1002/bdr2.1930
pmc: PMC8453706
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Monoclonal, Humanized
0
PCSK9 protein, human
EC 3.4.21.-
Proprotein Convertase 9
EC 3.4.21.-
alirocumab
PP0SHH6V16
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
1156-1160Informations de copyright
© 2021 The Authors. Birth Defects Research published by Wiley Periodicals LLC.
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