Long-Term Persistence With PCSK9 Inhibitors in Familial Hypercholesterolemia

Use of PCSK9 inhibitor therapy in patients with familial hypercholesterolemia improves quality of life.

In patients with familial hypercholesterolemia (FH), long-term persistence with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in a clinical care setting is quite high and is associated with a good quality of life (QOL), according to study results published in the European Journal of Preventive Cardiology.

Recognizing that persistence with chronic therapy is critical to reducing the burden of atherosclerotic cardiovascular disease (ASCVD) in patients with FH, the investigators sought to evaluate the persistence, efficacy, and impact on QOL of PCSK9 inhibitor treatment in this population. They conducted the open, multicenter, nationwide, long-term, prospective Spanish Familial Hypercholesterolemia cohort study (SAFEHEART; ClinicalTrials.gov Identifier: NCT02693548). Most individuals with the disorder require intensive lipid-lowering therapy (LLT), including PCSK9 inhibitors, to achieve current low-density lipoprotein cholesterol (LDL-C) goals. The SAFEHEART study was conducted among genetically defined patients with FH from Spain.

The study enrolled a total of 696 participants from 3759 heterozygous individuals with FH who were registered in the SAFEHEART cohort and had initiated PCSK9 inhibitor therapy. Of these patients, 51% received evolocumab and 49% received alirocumab. All patients were aged 18 years or older and 46% were women. The median participant age at initiation of treatment was 56.4 years (IQR, 49-66 years). Overall, 38% of patients had a history of ASCVD, 89% were receiving maximum tolerated LLT to reduce their LDL-C by 50%, and 50.4% were carrying a null allele variant.

The median LDL-C at initiation of PCSK9 inhibitor treatment was 145 mg/dL (IQR, 123-177 mg/dL). Following a median follow-up of 3.7 years (IQR, 2.3-4.8 years), and 27  participants discontinued PCSK9 inhibitor therapy, 5 permanently and 22 permanently. Persistence with PCSK9 inhibitor therapy was 96.1% in the entire treatment period.

Persistence with long-term PCSK9i treatment is very high in FH patients in clinical practice setting with a good related QOL.

The median LDL-C level after 1 year of PCSK9 inhibitor treatment was 63 mg/dL (IQR, 43-88 mg/dL), which remained constant until the last follow-up visit (61 mg/dL; IQR, 44-82 mg/dL). The median LDL-C percent reduction achieved after 1 year of treatment and at the last follow-up visit were 57.6% and 58%, respectively, compared with baseline levels (P <.001).

The 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) goals were achieved by 70% and 77% of individuals at 1 year and at the last follow-up visit, respectively (P <.001), whereas the 2019 ESC/EAS guideline goals were attained by 44.5% and 48% of individuals, respectively, in the same time periods (P =.01). The median QOL score increased slightly in the first year of the study and remained stable.

Several limitations of the study include a lack of blinding randomization. Further, blood testing in the follow-up period is not centralized, with testing being performed in lipid clinics according to national and international guidelines. Additionally, the results with respect to QOL cannot be compared with those from enrollment in SAFEHEART, since a different questionnaire was used initially and was not directly comparable with the EuroQoL.

“Persistence with long-term PCSK9i [inhibitor] treatment is very high in FH patients in clinical practice setting with a good related QOL,” the study authors wrote. “Furthermore, patients receiving PCSK9i on top of statins and ezetimibe vastly increases their LDL-C goals attainment.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Alonso R, Arroyo-Olivares R, Muñiz-Grijalvo O, et al; on behalf of SAFEHEART investigators. Persistence with long-term PCSK9 inhibitors treatment and its effectiveness in familial hypercholesterolemia: data from the SAFEHEART study. Eur J Prev Cardiol. Published online November 23, 2022. doi:10.1093/eurjpc/zwac277