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LDL-C Targets in Patients with Heterozygous Familial Hypercholesterolemia

Even with maximum intensity statin/ezetimibe treatment, most of the patients with familial hypercholesterolemia (FH) do not achieve the latest low-density lipoprotein cholesterol (LDL-C) targets; highlighting the necessity for proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) therapy and additional LDL-C lowering therapy.

Key Takeaway

  • In this cohort of patients with FH, only 2.7% had achieved the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) 2019-recommended LDL-C target.
  • More than half of FH patients (55.9%) would be eligible for add-on PCSK9i therapy despite receiving rosuvastatin/ezetimibe 40/10 mg/day.
  • Following theoretical administration of a PCSK9i, 42.4% of patients would still be eligible for additional LDL-C lowering therapies.

Why This Matters

  • ESC/EAS 2019 guidelines recommend more aggressive LDL-C targets for patients with FH.
  • PCSK9i are recommended in very high-risk patients with FH if the treatment goal is not attained on maximal tolerated statin plus ezetimibe and in FH patients who cannot tolerate statins.
  • However, it is currently unknown how many patient with FH are candidates for PCSK9i under 2019 ESC/EAS guidelines and in how many of them a fourth LDL-C lowering agent will be required.

Study Design

  • This study analyzed the data from Hellas-FH registry, which is based on a network of sites that are distributed throughout Greece.
  • Patients with at least a possible diagnosis of FH (Dutch Lipid Clinic Network [DLCN] score ≥3) were enrolled in the registry. Patients homozygous for FH were excluded.
  • Primary endpoint: Rate of LDL-C target achievement
  • Secondary endpoint: Impact of a theoretical treatment switch to rosuvastatin/ezetimibe 40/10 mg/day, and the rate of eligibility for PCSK9 inhibitor and the need for extra LDL-C lowering treatment.

Key Results

  • In total, 1,694 adult patients (860 male) were enrolled in this analysis, mean age of 50.8 ± 14.7 years old.
    • A total of 430 patients had established atherosclerotic cardiovascular disease.
    • Among patients, 61.4% (n = 1,040) had a target LDL-C of ≤55 mg/dL and the rest (38.6%, n = 654) a target of ≤70 mg/dL
    • Most treated patients were receiving a statin (97.5%) and about half were receiving additional ezetimibe (46.3%) and 4.9% were treated with a PCSK9i
  • On-treatment LDL-C was 130 ± 49 mg/dL (3.4 ± 1.3 mmol/L). Almost half of patients (47.3%) had an LDL-C reduction >50% than baseline.
    • When 2019 ESC/EAS guidelines were applied to an FH cohort, the LDL-C goals achievement was only 2.7%
    • In sub-group of patients with LDL-C targets of ≤55 mg/dL and ≤70 mg/dL, only 2.2% and 3.6% achieved target, respectively (P = 0.146 between groups)
  • After theoretical optimization of therapy to rosuvastatin/ezetimibe 40/10 mg daily, mean LDL-C level was 90 ± 26 mg/dL (2.3 ± 0.7 mmol/L).
    • Increase of ESC/EAS 2019 target achievement rate was 5.9%
    • In sub-group of patients with LDL-C targets of ≤55 mg/dL and ≤70 mg/dL, 3.0% and 10.8% achieved target, respectively (P <0.001 between groups)
    • Significant percentage of patients (55.9%) would be eligible for PCSK9i treatment despite receiving rosuvastatin/ezetimibe 40/10 mg
  • After theoretical administration of rosuvastatin/ezetimibe 40/10 mg plus PCSK9i (for those who were eligible):
    • LDL-C target achievement rate would rise to 57.6%
    • However, 42.4% of patients would still be eligible for further LDL-C lowering treatment
    • In sub-group analysis of patients with LDL-C targets of ≤55 mg/dL and ≤70 mg/dL, 86.3% and 10.8% achieved target, respectively (P < 0.001 between groups)
  • In subgroup of patients (n = 337) with DLCN score ≥9 (i.e., definitive diagnosis of FH).
    • Untreated LDL-C levels were 310 ± 90 mg/dL (8.0 ± 2.3 mmol/L)
    • Among patients already on treatment (n = 266), mean LDL-C was 147 ± 60 mg/dL (3.8 ± 1.6 mmol/L) with only 2.6% patients achieving the 2019 ESC/EAS LDL-C target
    • On switching all these patients not reaching LDL-C target as well as untreated patients to rosuvastatin/ezetimibe 40/10 mg, mean LDL-C was 112 ± 33 mg/dL (2.9 ± 0.9 mmol/L) and 3.3% patients reached target
      • 60.2% of patients with definite FH would be eligible for PCSK9i therapy despite receiving rosuvastatin/ezetimibe 40/10 mg versus 55.9% in the whole population.

Limitations

  • Diagnosis of FH was made using the DLCN criteria.
  • Participating sites were specialist outpatient lipid clinics.

Reference

  1. Rizos CV, Skoumas I, Rallidis L, Skalidis E, Tziomalos K, Garoufi A, et al. LDL cholesterol target achievement in heterozygous familial hypercholesterolemia patients according to 2019 ESC/EAS lipid guidelines: Implications for newer lipid-lowering treatments. Int J Cardiol. 2021;345:119-124. doi:10.1016/j.ijcard.2021.10.024. Epub ahead of print. PMID: 34687802.

 

MAT-KW-2200313/V2/OCT2023