HoFH International Clinical Collaboration – HICC

The HoFH International Clinical Collaboration (HICC) registry, launched in 2016, aims to create a formal international network of healthcare providers who manage HoFH patients that transcends the regional nature of current efforts. The registry has allowed collection of de-identified data relating to the clinical, genetic features and treatment of HoFH. This will provide insight into the prevalence, clinical consequences and treatment of HoFH and promote actions to improve current approaches to diagnosis and therapy.

In 2022

Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study

Tromp TR, Hartgers ML, Hovingh GK, et al. The Lancet; https://doi.org/10.1016/S0140-6736(21)02001-8.

Published Online January 28, 2022. Link: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02001-8/fulltext



Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally.


The HoFH International Clinical Collaborators registry collected data on patients with a clinical, or genetic, or both, diagnosis of HoFH using a retrospective cohort study design. This trial is registered with ClinicalTrials.gov, NCT04815005.


Overall, 751 patients from 38 countries were included, with 565 (75%) reporting biallelic pathogenic variants. The median age of diagnosis was 12·0 years (IQR 5·5–27·0) years. Of the 751 patients, 389 (52%) were female and 362 (48%) were male. Race was reported for 527 patients; 338 (64%) patients were White, 121 (23%) were Asian, and 68 (13%) were Black or mixed race. The major manifestations of ASCVD or aortic stenosis were already present in 65 (9%) of patients at diagnosis of HoFH. Globally, pretreatment LDL cholesterol levels were 14·7 mmol/L (IQR 11·6–18·4). Among patients with detailed therapeutic information, 491 (92%) of 534 received statins, 342 (64%) of 534 received ezetimibe, and 243 (39%) of 621 received lipoprotein apheresis. On-treatment LDL cholesterol levels were lower in high-income countries (3·93 mmol/L, IQR 2·6–5·8) versus non-high-income countries (9·3 mmol/L, 6·7–12·7), with greater use of three or more lipid-lowering therapies (LLT; high-income 66% vs non-high-income 24%) and consequently more patients attaining guideline-recommended LDL cholesterol goals (high-income 21% vs non-high-income 3%). A first major adverse cardiovascular event occurred a decade earlier in non-high-income countries, at a median age of 24·5 years (IQR 17·0–34·5) versus 37·0 years (29·0–49·0) in high-income countries (adjusted hazard ratio 1·64, 95% CI 1·13–2·38).


Worldwide, patients with HoFH are diagnosed too late, undertreated, and at high premature ASCVD risk. Greater use of multi-LLT regimens is associated with lower LDL cholesterol levels and better outcomes. Significant global disparities exist in treatment regimens, control of LDL cholesterol levels, and cardiovascular event-free survival, which demands a critical re-evaluation of global health policy to reduce inequalities and improve outcomes for all patients with HoFH.


Amsterdam University Medical Centers, Location Academic Medical Center; Perelman School of Medicine at the University of Pennsylvania; and European Atherosclerosis Society

In 2021

89th EAS Congress, Helsinki

HICC reports

The unveiling of posters at EAS Helsinki 2021 provided important news from the EAS-led Homozygous familial hypercholesterolaemia International Clinical Collaboration (HICC) registry, the largest global database of homozygous familial hypercholesterolaemia (HoFH) patients (1). HoFH is the most severe form of FH, thought to affect about one in 300,000 to one in a million people, and is characterised by extremely high levels of low-density lipoprotein cholesterol (LDL-C) from birth and severe atherosclerotic cardiovascular disease (2). Many patients may have their first heart attack in childhood (2).

The HICC was launched in 2016 aiming to provide data about the prevalence, clinical consequences and treatment of HoFH, as well as promote actions to improve care. Patients are included in the registry based on clinical or genetic criteria for HoFH.

This latest report provides data on 765 patients from 38 countries world-wide, the majority (75%) diagnosed by genetic criteria. Categorising the data by high-income countries (n=410) versus non-high-income countries (n = 355) revealed disparities in FH care.

According to Professor Derick Raal, co-coordinator of the HICC Registry (University of the Witwatersrand, Johannesburg, South Africa): ‘These new findings from the HICC Registry underline the need for action to ensure equity in care for this rare, severe condition, crucial to improve prognosis and freedom from early heart attack, often during childhood.’

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While patients from non-high-income countries were diagnosed earlier than those in high-income countries (median 10 versus 16 years), access to novel treatments which are now part of the armamentarium of managing HoFH was much more limited. Among non-high-income countries, significantly fewer patients received PCSK9 inhibitors (17% versus 25% in high-income countries, p<0.001) and lomitapide (2% versus 13%, p<0.001), and no patients (versus 4.3%) received evinacumab. Consequently on-treatment LDL-C levels were much higher for patients in lower-income countries, about double those in high-income regions (mean 9.6 versus 4.7 mmol/L, p<0.001). Overall, while only a minority of patients attained guideline-recommended LDL-C goal, almost none were in non-high-income countries (2.6% versus 21.4% in high-income countries, p<0.001). 

Importantly, limited access to novel therapies and higher on-treatment LDL-C levels significantly impacted outcome. The cardiovascular burden of HoFH was greater among non-high-income countries, with earlier onset of major coronary events (median 24 versus 35 years) and younger age of cardiovascular death (median 24 versus 40 years). Thus, inequity in treatment almost halved the age of death due to cardiovascular causes among patients in non-high-income regions.

In conclusion, patients in high-income countries had access to novel lipid-lowering therapies more frequently, attained lower LDL-C levels and had longer event-free survival. These new findings from the HICC reinforce the value of this global registry for highlighting inequities in resource allocation for FH care, in particular the limited availability of contemporary and novel therapies. Going forward, this information will be critical in discussions with all stakeholders in FH care.


  1. Tromp TR, Hartgers ML, Hovingh GK, et al. Worldwide perspective on homozygous familial hypercholesterolemia diagnosis, treatment and outcome – Results from the HICC Registry. Poster session. Presented at EAS Helsinki 2021 Virtual – 30th May -2 June 2021.
  2. Cuchel M, Bruckert E, Ginsberg HN, et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J 2014;35:2146-57.