Global HICC registry highlights persistent gaps in diagnosis and treatment of HoFH

The global HICC registry shows that homozygous familial hypercholesterolemia (HoFH) remains associated with premature ASCVD and early mortality despite advances in lipid-lowering therapy, underscoring the need for earlier diagnosis and equitable access to intensive treatment.

This summary is based on the publication of Schonck WAM, Mulder JWCM, Cuchel M - Homozygous familial hypercholesterolaemia: insights from the Global HICC Registry. Eur Heart J. 2026 May 18:ehag357. [Online ahead of print]. doi: 10.1093/eurheartj/ehag357.

Introduction and methods

Background

Homozygous familial hypercholesterolemia (HoFH) is a rare inherited disorder characterized by extremely elevated LDL-c levels from birth, resulting in a markedly increased risk of premature ASCVD [1-2]. Although several novel lipid-lowering therapies have become available in recent years, real-world data on the diagnosis, treatment, and outcomes of patients with HoFH remain limited worldwide.

Aim of the review

This review summarizes key findings from the global HoFH International Clinical Collaborators (HICC) registry and highlights remaining knowledge gaps and future directions for improving the care of patients with HoFH.

HICC registry

The HICC registry is an international observational registry that currently includes data from more than 950 patients with HoFH treated at over 90 institutions in 45 countries. The registry captures demographic, genetic, clinical, treatment, and cardiovascular outcome data to evaluate the contemporary management of HoFH.

Main findings

Clinical presentation

• Median age at diagnosis was 12 years (IQR: 5.5–27.0).
• Median untreated LDL-c concentration was 14.7 mmol/L (IQR: 11.6–18.4).
• At diagnosis, 9% of patients had already developed ASCVD or (supra)aortic valve disease.

Lipid-lowering therapy

• Despite widespread use of statins (92%), ezetimibe (64%), and lipoprotein apheresis (39%), median treated LDL-c remained 7.7 mmol/L (IQR: 4.6–11.5).
• Only 4% of patients achieved guideline-recommended LDL-c targets.
• Early initiation of lipoprotein apheresis in childhood was associated with greater LDL-c reductions and longer ASCVD-free survival.

Cardiovascular burden

• Median age at first MACE was 31 years (IQR: 22–42).
• Median age at death was 37 years, demonstrating that HoFH remains a life-limiting disease despite current therapies.
• Patients with LDLR null variants had more severe disease than those with LDLR defective variants.

Sex differences

• No differences between women and men were observed in age at diagnosis, untreated or treated LDL-c levels, treatment intensity, or age at onset of ASCVD.

Global disparities in care

• Marked differences in access to genetic testing and novel lipid-lowering therapies were observed between high-income and non-high-income countries.
• Patients from non-high-income countries had substantially higher treated LDL-c levels, were less likely to receive three or more lipid-lowering therapy, and achieved LDL-c targets less frequently than patients from high-income countries.
• The median age at first MACE was approximately 12 years younger in non-high-income than in high-income countries (24.5 vs. 37.0 years).

Future directions

The authors recommend several strategies to improve the care of patients with HoFH worldwide:

• Expanding early detection through broader lipid and genetic screening, including population-based childhood screening and potentially universal newborn screening.
• Improving global access to intensive lipid-lowering therapies, particularly newer LDLR-independent treatments, and promoting earlier, genotype-informed treatment strategies.
• Addressing evidence gaps by prioritizing research on pediatric management, aortic valve disease, reproductive health, advanced imaging, and long-term outcomes of emerging therapies.
• Integrate patient perspectives by incorporating patient-reported outcomes and treatment burden into research and care.
• Support the continued growth of the HICC registry and foster international collaboration to promote knowledge exchange, multidisciplinary care, and the dissemination of best practices.

Conclusion

The HICC registry provides the largest contemporary global overview of patients with HoFH and demonstrates that delayed diagnosis, poor LDL-c goal attainment, unequal access to advanced lipid-lowering therapies, and substantial premature cardiovascular morbidity and mortality remain major challenges. The authors conclude that earlier diagnosis, more intensive lipid-lowering treatment, and greater global equity in access to care are essential to improve outcomes in patients with HoFH.

Find this article online at Eur Heart J.

References

1. Tromp TR, Hartgers ML, Hovingh GK, Vallejo-Vaz AJ, Ray KK, Soran H, et al. Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study. Lancet 2022;399:719–28. https://doi.org/10.1016/S0140-6736(21)02001-8
2. Cuchel M, Raal FJ, Hegele RA, Al-Rasadi K, Arca M, Averna M, et al. 2023 up date on European atherosclerosis society consensus statement on homozygous familial hypercholesterolaemia: new treatments and clinical guidance. Eur Heart J 2023;44:2277–91. https://doi.org/10.1093/eurheartj/ehad197