von Willebrand factor inhibition improves endothelial function in patients with stable angina

J Cardiovasc Transl Res. 2013 Jun;6(3):364-70. doi: 10.1007/s12265-012-9422-3. Epub 2012 Dec 12.

Abstract

ALX-0081 is a novel nano-antibody inhibiting von Willebrand factor (vWF). We evaluated whether direct inhibition of vWF by ALX-0081 improves endothelial function. Stable patients (pts, n = 55) with single vessel disease undergoing percutaneous coronary intervention (PCI) were randomized to ALX-0081 (n = 38) or placebo (n = 17). vWF inhibition was assessed by vWF antigen level (vWF:Ag) and activity by ristocetin test (vWF:RiCo). Endothelial function was assessed before (BL), 6 h and 24 h after PCI by: (a) endothelial peripheral arterial tonometry (Endoscore); (b) endothelial microparticles (EMPs) by flow cytometry. vWF:Ag and vWF:RiCo decreased within 1 h from ALX-0081. In the placebo group, no significant Endoscore changes occurred from BL to 24 h. In ALX-0081 group, Endoscore increased from BL to 24 h (p = 0.014). A decrease in EMPs was observed after ALX-0081 (p < 0.01), while no changes occurred in placebo pts. An inhibition of vWF with ALX-0081 significantly improves peripheral endothelial function.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Angina, Stable / blood
  • Angina, Stable / immunology
  • Angina, Stable / therapy*
  • Belgium
  • Biomarkers / blood
  • Cell-Derived Microparticles / drug effects
  • Cell-Derived Microparticles / metabolism
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / immunology
  • Coronary Artery Disease / therapy*
  • Double-Blind Method
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology
  • Female
  • Flow Cytometry
  • Hemodynamics / drug effects
  • Humans
  • Male
  • Manometry
  • Middle Aged
  • Molecular Sequence Data
  • Percutaneous Coronary Intervention* / adverse effects
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prospective Studies
  • Single-Domain Antibodies / adverse effects
  • Single-Domain Antibodies / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • von Willebrand Factor / antagonists & inhibitors*
  • von Willebrand Factor / immunology
  • von Willebrand Factor / metabolism

Substances

  • Biomarkers
  • Platelet Aggregation Inhibitors
  • Single-Domain Antibodies
  • von Willebrand Factor
  • caplacizumab

Associated data

  • EudraCT/2007-007263-24