Adjusting Multimodal Lipid-Lowering Therapy in bi-Allelic Familial Hypercholesterolemia

Multimodal lipid lowering therapy may be regularly adjusted in patients with bi-allelic familial hypercholesterolemia based on ultrasounds of all accessible arteries.

Multimodal lipid lowering therapy (LLT) may be regularly adjusted in patients with bi-allelic familial hypercholesterolemia (FH) based on ultrasounds of all accessible arteries, according to a study published in The American Journal of Cardiology.

In this observational, retrospective and partially prospective multicenter study, 24 patients with FH treated with statis, ezetimibe, or both who were approved for chronic lipoprotein apheresis (LA) before age 15 were recruited from 14 specialized treatment centers across Germany. All patients had a family history of atherosclerotic cardiovascular disease (ASCVD) and bi-allelic mutations which partially or completely impaired their low-density lipoprotein (LDL) receptor activity. Patient medical records were examined to assess treatment details and disease progression.

In this cohort, the average age of FH diagnosis was 6.3±3.4 years, and mean LDL cholesterol (LDL-C) concentration at time of diagnosis was 752±193 mg/dl. The average age at LA therapy initiation was 8.5±3.1 years and LA treatment was maintained, prior to study onset for 8.7±6.7 years.

Chronic LA resulted in a mean reduction of 75.5% of LDL-C levels from 246±98 mg/dl to 72±36 mg/dl. A dual therapy of LA and lipid-lowering medications reduced LDL-C concentration below the pediatric target (135 mg/dl) in 46% of patients.

LA therapy prevented cardiovascular events in 67% of participants who did not require vascular or surgical interventions. However, 14 of these patients had subclinical ASCVD.

Among the patients who were less responsive to LA therapy, 38% exhibited clinically relevant ASCVD progression. Three patients had a myocardial infarction, 1 had a pulmonary embolism, 1 patient had rapidly progressing ASCVD at the start of LA therapy, and died 2.5 years after starting weekly LA regimen.

Pathogenic complications at the aortic valve were observed in 79% of patients. A total of 75.0% of patients had aortic valve regurgitation, 21.7% had dysplastic and functional bicuspid aortic valve, and 41.7% had aortic valve stenosis. These complications led to aortic valve replacement in 8.3% of patients.

A total of 13,500 LA treatment sessions were examined during the study period (217.1 patient-years.) Overall, chronic LA therapy in 1 or 2 sessions per week was well tolerated. The most common difficulty experienced was related to vascular access, particularly in young children. Of 25 participants, 20 required an arteriovenous fistula.

A major limitation of this study was the small cohort due to the rarity of this pathology.

“LA still appears indispensable for patients with bi-allelic FH and severe hypercholesterolemia to maximize the reduction of LDL-C,” concluded the study authors. “Regular standardized assessment of both the AV, and all arteries which are accessible by ultrasound should be performed to adjust the intensity of multimodal LLT with the goal to prevent ASCVD progression, potentially leading to serious clinical sequelae.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Taylan C, Driemeyer J, Schmitt C P, et al. Cardiovascular outcome of pediatric patients with bi-allelic (homozygous) familial hypercholesterolemia before and after initiation of multimodal lipid lowering therapy including lipoprotein apheresis. Am J Cardiol. 2020;S0002-9149(20)30952-8. doi:10.1016/j.amjard.2020.09.015