Persistence with long-term PCSK9 inhibitor treatment and its effectiveness in familial hypercholesterolaemia: data from the SAFEHEART study

Eur J Prev Cardiol. 2023 Mar 1;30(4):320-328. doi: 10.1093/eurjpc/zwac277.


Aims: Most heterozygous familial hypercholesterolaemia (FH) patients require intensive lipid-lowering therapy (LLT) including PCSK9 inhibitors (PCSK9is) to reach current low-density lipoprotein cholesterol (LDL-C) goals. Persistence with chronic treatment is important to reduce the burden of atherosclerotic cardiovascular disease. We analysed persistence, efficacy, and impact on quality of life (QoL) of PCSK9i in FH patients in clinical practice setting.

Methods and results: Spanish Familial Hypercholesterolaemia Cohort Study (SAFEHEART) is an open, prospective study in genetically defined FH patients in Spain. Patients ≥18 years of age (n = 696, 46% females) on stable LLT treated with PCSK9i were analysed. Median LDL-C at starting PCSK9i was 145 mg/dL [interquartile range (IQR), 123-177], 3.8 mmol/L (IQR 3.2-4.6). After a median follow up of 3.7 years (IQR 2.3-4.8), 27 patients (4%) discontinued PCSK9i treatment: 5 temporarily (0.7%) and 22 permanently (3.2%). Persistence with PCSK9i was 96.1% in the whole period. Median LDL-C levels and % LDL-C reduction attained after 1 year of treatment and in the last follow-up visit were 63 mg/dL (IQR 43-88), 1.6 mmol/L (IQR 1.1-2.23); 61 mg/dL (IQR 44-82), 1.6 mmol/L (IQR 1.1-2.1); 57.6% (IQR 39.5-69); and 58% (IQR 44-68), respectively. 2016 and 2019 ESC/EAS LDL-C goals were attained by 77 and 48% of patients, respectively, at the last follow-up visit (P < 0.001). Mean QoL score increased slightly in the first year and remained stable.

Conclusion: Long-term persistence with PCSK9i in FH patients is very high, with a good QoL. Effectiveness in LDL-C reduction and LDL-C goal achievement dramatically improved with PCSK9i in this high-risk population in clinical practice setting.

Trial registration: number NCT02693548.

Keywords: Familial hypercholesterolaemia; LDL-C targets; Lipid-lowering treatment; PCSK9 inhibitors; Persistence; Statins.

MeSH terms

  • Anticholesteremic Agents* / therapeutic use
  • Cholesterol, LDL
  • Cohort Studies
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Hyperlipoproteinemia Type II* / drug therapy
  • Male
  • PCSK9 Inhibitors
  • Proprotein Convertase 9
  • Prospective Studies
  • Quality of Life


  • PCSK9 Inhibitors
  • Cholesterol, LDL
  • Anticholesteremic Agents
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors

Associated data