PCSK9 inhibitors revisited: Effectiveness and safety of PCSK9 inhibitors in a real-life Spanish cohort

Biomed Pharmacother. 2022 Feb:146:112519. doi: 10.1016/j.biopha.2021.112519. Epub 2021 Dec 28.

Abstract

Introduction: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have emerged as a therapeutic option for patients with hypercholesterolemia who do not attain low-density lipoprotein cholesterol (LDL-C) goals and/or are intolerant to other lipid-lowering drugs. Our aim was to analyze the effectiveness and safety of PCSK9i in routine clinical practice and factors related to poor outcomes.

Materials and methods: We conducted an ambispective study in 115 patients who recieved alirocumab or evolocumab, in a tertiary level hospital. From February 2017 to April 2020, patients were recruited and followed up for a median of 20.4 months. The main outcomes were relative reduction in LDL-C, percentage of patients achieving the therapeutic goals established by 2016 ESC/EAS guidelines, incidence of major cardiovascular events (MACEs) and drug-related adverse events (ADRs).

Results: The median LDL-C achieved was 57.0 mg/dL (relative reduction of 59.9% from baseline, p< 0.001). After adjusting for confounders, smaller LDL-C reductions were related to female sex, absence of concomitant lipid-lowering therapy and treatment with alirocumab. Overall, 84.6% of the patients achieved the therapeutic goals. During follow-up, 7 MACEs were detected. ADRs, generally considered mild, affected 38.1% of the participants (mainly mialgias and arthralgias) and triggered discontinuations in 8.7% of cases.

Conclusions: PCSK9i are effective and safe, although certain factors may influence their effectiveness. Interestingly, our results suggest that alirocumab and evolocumab may not be therapeutic equivalents, as initially suggested.

Keywords: Alirocumab; Effectiveness; Evolocumab; PCSK9 inhibitors; Safety.

MeSH terms

  • Age Factors
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / adverse effects
  • Anticholesteremic Agents / therapeutic use*
  • Cardiovascular Diseases / epidemiology
  • Comorbidity
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hypercholesterolemia / drug therapy*
  • Life Style
  • Lipids / blood
  • Male
  • Middle Aged
  • PCSK9 Inhibitors / administration & dosage
  • PCSK9 Inhibitors / adverse effects
  • PCSK9 Inhibitors / therapeutic use*
  • Sex Factors
  • Spain

Substances

  • Antibodies, Monoclonal, Humanized
  • Anticholesteremic Agents
  • Lipids
  • PCSK9 Inhibitors
  • evolocumab
  • alirocumab