Marked plaque regression in homozygous familial hypercholesterolemia

Area of Science:

• Cardiology
• Genetics
• Pharmacology

Background:

• Homozygous familial hypercholesterolemia (HoFH) is characterized by extremely elevated LDL cholesterol and premature cardiovascular disease risk.
• Atherosclerotic plaques are common in young HoFH patients due to the genetic nature of the condition.
• The potential for plaque regression with intensive lipid-lowering strategies in adolescent HoFH patients remains largely unknown.

Purpose of the Study:

• To investigate the effect of intensive lipid-lowering therapy, including evinacumab, on atherosclerotic plaque regression in adolescent HoFH patients.
• To assess the feasibility of plaque regression in young patients with severe HoFH.

Main Methods:

• Two HoFH patients with null/null LDLR variants were treated with evinacumab (anti-ANGPTL3 antibody) as part of a clinical trial.
• Patients received concurrent treatment with statins, ezetimibe, and weekly LDL apheresis.
• Coronary computed tomography angiography (CCTA) was performed before and after 6 months of evinacumab treatment to evaluate plaque volume.

Main Results:

• Evinacumab significantly reduced pre-apheresis LDL cholesterol levels from >5.0 mmol/l to ~2.3 mmol/l and post-apheresis levels from >1.3 mmol/l to ~0.8 mmol/l.
• Total atherosclerotic plaque volumes decreased substantially, by 76% in a 12-year-old and 85% in a 16-year-old patient.
• These reductions were observed after 6 months of combined intensive lipid-lowering therapy.

Conclusions:

• Intensive lipid-lowering therapy, including evinacumab, can lead to profound atherosclerotic plaque reduction in severely affected young HoFH patients.
• This study demonstrates that atherosclerotic plaques can regress in adolescent HoFH patients, even with severe genetic lipid disorders.
• The findings suggest that early and aggressive treatment can impact plaque burden in young HoFH individuals.