Introduction: Familial hypercholesterolemia (FH) is a genetic condition associated with elevated cholesterol levels and increased risk of atherosclerotic cardiovascular diseases. Lipid-lowering drugs, i.e. statins, ezetimibe and PCSK9 inhibitors (PCSK9inh) are most often combined for effective treatment of FH. While statins may be continued during pregnancy if deemed necessary, other lipid-lowering drugs lack safety data leaving little pharmacological therapeutic options in pregnancies with FH. Thus, guidelines recommend withdrawing lipid-lowering drugs, ideally pre-conception, followed by lipid apheresis.
Clinical case: A 28-year old female patient was diagnosed with FH in the face of total cholesterol level of 17.0 mmol/L (657 mg/dL), HDL-cholesterol 2.6 mmol/L (101 mg/dL), triglycerides 1.2 mmol/L (106 mg/dL) and LDL-cholesterol 14.6 mmol/L (14.6 mg/dL). The three-vessel coronary heart disease was treated by coronary artery bypass graft (CABG) and drug-eluting stents, with a sequential introduction of rosuvastatin, ezetimibe and alirocumab at maximal dosage. Genetic testing confirmed compound heterozygous LDLRmutation, in addition to elevated Lp(a) at 1150 mg/L. While the patient was planning a future pregnancy, she was advised to use contraceptives for at least 12 months post-CABG. Pre-conception drug withdrawal was planned, followed by a bridge to lipid apheresis, such as the Direct Adsorption of Lipoproteins (DALI) technique. Meanwhile, an unplanned pregnancy led us to stop all medications abruptly at 6 gestational weeks, except for aspirin. DALI allowed the control of LDL-cholesterol in the range of 4.97.9 mmol/L (189305 mg/dL, before DALI session) to 1.23.2 mmol/L (46124 mg/dL, after DALI session). This first required weekly sessions, then the frequency was increased to twice weekly for the third trimester. The regular pregnancy ultrasounds highlighted an isolated agenesis of the corpus callosum with a normal CGH array and confirmed by fetal magnetic resonance imaging. No first trimester exposure to PCSK9inh has been reported so far. At the time of the ECE meeting, we will be able to report the outcome of the pregnancy, the DALI efficacy and the first neonatal evaluation of this at-risk pregnancy, with an assessment of the accountability of the reported treatment in the observed malformation.
Discussion: Lipid apheresis should be discussed with all female patients of childbearing age with FH. Guidelines do not specifically recommend preconception measures to optimize the fetal development and lower maternal risks. Pharmacovigilance in the era of PCSK9inh for FH requires more data on their potential fetal effects in humans.
18 - 21 May 2019
European Society of Endocrinology