Contemporary lipid-lowering management and risk of cardiovascular events in homozygous familial hypercholesterolaemia: insights from the Italian LIPIGEN Registry

Eur J Prev Cardiol. 2024 Jun 3;31(8):1038-1047. doi: 10.1093/eurjpc/zwae036.

Abstract

Aims: The availability of novel lipid-lowering therapies (LLTs) has remarkably changed the clinical management of homozygous familial hypercholesterolaemia (HoFH). The impact of these advances was evaluated in a cohort of 139 HoFH patients followed in a real-world clinical setting.

Methods and results: The clinical characteristics of 139 HoFH patients, along with information about LLTs and low-density lipoprotein cholesterol (LDL-C) levels at baseline and after a median follow-up of 5 years, were retrospectively retrieved from the records of patients enrolled in the LIPid transport disorders Italian GEnetic Network-Familial Hypercholesterolaemia (LIPIGEN-FH) Registry. The annual rates of major atherosclerotic cardiovascular events (MACE-plus) during follow-up were compared before and after baseline. Additionally, the lifelong survival free from MACE-plus was compared with that of the historical LIPIGEN HoFH cohort. At baseline, LDL-C level was 332 ± 138 mg/dL. During follow-up, the potency of LLTs was enhanced and, at the last visit, 15.8% of patients were taking quadruple therapy. Consistently, LDL-C decreased to an average value of 124 mg/dL corresponding to a 58.3% reduction (Pt < 0.001), with the lowest value (∼90 mg/dL) reached in patients receiving proprotein convertase subtilisin/kexin type 9 inhibitors and lomitapide and/or evinacumab as add-on therapies. The average annual MACE-plus rate in the 5-year follow-up was significantly lower than that observed during the 5 years before baseline visit (21.7 vs. 56.5 per 1000 patients/year; P = 0.0016).

Conclusion: Our findings indicate that the combination of novel and conventional LLTs significantly improved LDL-C control with a signal of better cardiovascular prognosis in HoFH patients. Overall, these results advocate the use of intensive, multidrug LLTs to effectively manage HoFH.

Keywords: Cardiovascular risk; Evinacumab; Homozygous familial hypercholesterolaemia; Lipid-lowering therapies; Lomitapide; PCSK9 inhibitors; Real-world.

Plain language summary

Contemporary real-world data from the Italian cohort of patients affected by homozygous familial hypercholesterolaemia demonstrated that the addition of novel, low-density lipoprotein receptor (LDLR)-independent medications to conventional therapies allowed the achievement of unprecedented low-density lipoprotein cholesterol (LDL-C) values with a trend towards a reduction of cardiovascular risk.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Anticholesteremic Agents / therapeutic use
  • Biomarkers / blood
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control
  • Cholesterol, LDL* / blood
  • Female
  • Genetic Predisposition to Disease
  • Homozygote
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hyperlipoproteinemia Type II* / blood
  • Hyperlipoproteinemia Type II* / diagnosis
  • Hyperlipoproteinemia Type II* / drug therapy
  • Hyperlipoproteinemia Type II* / genetics
  • Hypolipidemic Agents / therapeutic use
  • Italy / epidemiology
  • Male
  • Middle Aged
  • PCSK9 Inhibitors / therapeutic use
  • Registries*
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Cholesterol, LDL
  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Anticholesteremic Agents
  • PCSK9 Inhibitors
  • Hypolipidemic Agents

Grants and funding