Clinical practice experience in patients with familial hypercholesterolemia (FH) from the Safeheart registry

Key Takeaway

In clinical practice, PCSK9i (alirocumab or evolocumab) on top of maximum LLT significantly reduced LDL-C levels (by 58%) and improved LDL-C target achievement in patients with heterozygous FH (both in men and women).

LDL-C goals*:

•  2016 ESC/EAS goals†: Patients with ASCVD = 67%; patients without ASCVD = 80%
•  2019 ESC/EAS LDL-C goals‡: VHR patients = 46%; HR patients = 50%

Independent predictors for LDL-C goals: Male gender; smoking; and use of statins + ezetimibe

Why This Matters

• ^§ Use of PCSK9i in clinical practice is less frequent (partly due to cost and insurance issues).
• Safeheart registry study assessed the use and efficacy of PCSK9i as well as LDL-C goals attainment in clinical practice setting of FH patients.

Study Design

Safeheart: Open, Multicenter, Nationwide, Long-term Prospective Study (N = 433 [Alirocumab = 211; Evolocumab = 222])

Key Inclusion Criteria

Patients with molecular diagnosis of FH (aged ≥20 years) on stable LLT, who received PCSK9i (alirocumab 75/150 mg every 2 or 4 weeks, or evolocumab 140 mg every 2 weeks or 420 mg every 4 weeks) from 2016 to January 2020^¶

Key Exclusion Criteria

Patients who participated in RCTs with PCSK9i before 2016

LDL-C Goals: Defined and analyzed based on 2016 and 2019 ESC/EAS guidelines

Key Results

Overall, 433 patients were included in the analysis

Mean age = 55 years; male = 53%; history of ASCVD = 39%; median follow-up = 2.5 years

LDL-C Levels:

• Before PCSK9i: Median LDL-C = 145 mg/dL (IQR: 125–173)
• After addition of PCSK9i: LDL-C levels reduced by 58% (IQR: 41–70 [P <0.001]) in men and women without differences between both PCSK9i 
  Median LDL-C = 62 mg/dL (IQR: 44–87)

LDL-C Goals*

• 2016 ESC/EAS goals†: Patients with ASCVD = 67%; patients without ASCVD = 80%
• 2019 ESC/EAS LDL-C goals‡: VHR patients = 46%; HR patients = 50%
• Higher LDL-C levels before PCSK9i initiation had a significant inverse relationship with goals attainment

Independent Predictors (2019 ESC/EAS LDL-C GOALS)

• Male gender (P = 0.023); smoking (P = 0.041); and use of statins + ezetimibe (P = 0.008)

Limitations

• Study lacked blinding randomization
• Follow-up analysis was not centralize
• In the follow-up analysis, Lp(a) measurement was not available

* Without differences between alirocumab or evolocumab.
^† LDL-C target below 70 mg/dL and 100 mg/dL, respectively according to 2016 ESC/EAS guidelines.
^‡ LDL-C goal according to 2019 ESC/EAS guidelines (for VHR patients <55 mg/dL; for HR patients <70 mg/dL).
^§ International guidelines recommend PCSK9i for patients with FH with substantially higher LDL-C levels despite maximally tolerated statin ± ezetimibe.
^¶ Kept a stable dose of PCSK9i at least 3 months before the last analysis. PCSK9i eligibility was based on Spanish National Health System reimbursement regulations in FH patients.