Effectiveness and safety of PCSK9 inhibitors in Czech real-world practice

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) were effective and well-tolerated, with sustained effects, comparable to those in randomized studies.

Key Takeaway

  • PCSK9i were effective in statin-intolerant patients, as significantly lower levels of low-density lipoprotein-cholesterol (LDL-C) were seen within 12 weeks.
  • Target LDL-C levels were attained by 35.9% of patients in primary atherosclerotic cardiovascular disease (ASCVD) prevention and 65.7% of those in secondary ASCVD prevention at 1 year after therapy initiation.

Why This Matters

  • In patients with ASCVD with insufficient response or intolerant to traditional LDL-C-lowering therapies, PCSK9i can be beneficial.
  • The extent to which the outcomes of therapy with PCSK9i in Czech real-world practice was comparable with those reported by large, randomized studies involving Czech patients was unknown.

Study Design

  • The effect of PCSK9i therapy was assessed in the entire study population (N = 314; men = 44%; mean age = 63 years) in a Prague-based center of preventive cardiology between 31 July 2018 and 30 September 2020, including in the following subgroups of patients:
    • With familial hypercholesterolemia (FH, 65%) vs. without FH, with LDL-C levels ≥4 mmol/L despite maximum tolerated dose (MTD) of statin
      • Ezetimibe was given as an add-on, except if LDL-C levels were >50% than target if statin-naïve, or >20% if on statin at MTD
    • With FH in primary (69%) or secondary (31%) ASCVD prevention, with LDL-C levels ≥3 mmol/L, despite lipid-lowering therapy at MTD
      • Without FH in secondary ASCVD prevention (n = 107)
    • On PCSK9i monotherapy alone vs. PCSK9i in combination with a statin
  • Potential differences in the effect and tolerability of alirocumab (75 mg or 150 mg; n = 113) and evolocumab (140 mg; n = 156) were also assessed.
  • Primary endpoints: Change in LDL-C, total cholesterol (TC), lipoprotein (a) Lp(a), apolipoprotein B (apoB), high-density lipoprotein-cholesterol (HDL-C), and triglycerides (Tg) at 12 and 24 weeks, and 1 and 2 years after initiation of therapy with PCSK9i
  • Secondary endpoints: Impact on glucose metabolism

Key Results

Effect on lipid parameters

  • Changes in LDL-C levels: There was a significant reduction at 12 weeks (−59.4%) that continued to persist at 2 years (−62.6%)
  • Changes in TC levels: There was a significant reduction at 12 weeks (decrease by 41.7%) and at 2 years (decrease by 43.9%)
  • Changes in Lp(a) levels: There was a reduction at 12 weeks (−25.4%) and a further reduction at 24 weeks (−35.5%)
  • Changes in apoB levels: There was a significant reduction at 12 weeks (54.2%) and at 2 years (58.1%)
  • Changes in HDL-C levels: There was a slight increase at 12 weeks (4%) and at 2 years (5.6%)
  • Changes in Tg levels: There was a significant reduction at 2 years (−30.3%), with levels reaching targets set by the 2019 ESC/EAS guidelines


Effect on glucose parameters

  • Glucose metabolism was not affected by PCSK9i therapy


Effect on patients with and without FH

  • Dynamics of decrease after therapy initiation were similar, with a decrease in LDL-C levels by 56.7% and 61.8% at 12 and 24 weeks in patients with FH compared to 67.4% and 68.8% in patients without FH, respectively
  • At 2 years, significantly lower LDL-C levels were observed in both patients with FH (−63.5%) and those without FH (−62.3%)


Effect on patients with primary and secondary ASCVD prevention

  • Dynamics of decrease after therapy initiation were similar, with a decrease in LDL-C levels by 55.7% and 61.5% at 12 and 24 weeks in patients in primary prevention, and by 63.9% and 66.3% in those in secondary prevention
  • At 2 years, significantly lower LDL-C levels were observed in both patients in primary (−61.7%) and secondary (−64.2%) prevention


Effect on patients tolerant vs intolerant to statins

  • By week 12, LDL-C levels in patients on maximum statin dose decreased by 65.2% compared to 55% in those not on statin therapy
  • At 2 years, significant differences in LDL-C levels were seen between patients on maximum statin dose vs those who were statin-intolerant (64% vs 59.3%)


Effect on patients treated with alirocumab vs evolocumab

  • By week 12, LDL-C levels in patients on alirocumab decreased by 55.5% compared to 66.1% in patients on evolocumab
  • At 2 years, significant differences in LDL-C levels were seen (64.7% vs 61%) Correlation between baseline LDL-C levels and their decrease relative to therapy


Correlation between baseline LDL-C levels and their decrease relative to therapy

  • Moderately strong inverse correlation (Pearson’s r = −0.7147) was seen


Effect on safety

  • Side effects were reported by 9% of patients (alirocumab-related: 14; evolocumab-related: 16); 15 patients withdrew due to side effects
  • Flu-like syndrome was more frequent (n = 13), followed by pain at injection site (n = 5), myalgia (n = 5), and gastrointestinal intolerance (n = 3)

Limitations

  • Patients were enrolled only from a single center and those not meeting the reimbursement criteria and self-payers were not included.
  • Cardiovascular effects of PCSK9i were not assessed
  • Patients were enrolled only if diagnosed with FH or statin intolerance, two indications for which reimbursement for treatment is permitted.
    1. Altschmiedová T, Todorovová V, Šnejdrlová M, Šatný M, Češka R. PCSK9 inhibitors in real-world practice: Analysis of data from 314 patients and 2 years of experience in a center of preventive cardiology. Curr Atheroscler Rep. 2022 May;24(5):357–363. doi: 10.1007/s11883-022-01008-8. PMID: 35332442.

MAT-KW-2200329/V1/NOV2022