Ischaemic stroke after exposure to aflibercept: interaction with vitamin K antagonist and/or direct pharmacodynamic effect?
OBJECTIVE
Vascular endothelial growth factor (VEGF) proteins are involved in the regulation of vascular endothelium, and their inhibition led to the development of a number of drugs used for malignancies or exudative neo-vascular age-related macular degeneration (AMD).


METHODS
We report a case of ischemic stroke in an 87-year-old woman having received intravitreal aflibercept, a new anti-VEGF for AMD. She had been treated with ranibizumab since 2007. In 2013, ranibizumab was replaced with aflibercept, followed by a decrease in the International Normalized Ratio, complicated by a stroke a few days later. The rechallenge was positive.


CONCLUSIONS
A potential time-dependent interaction between aflibercept and VKA antagonist and/or a direct effect of aflibercept may have contributed to the occurrence of the ischaemic stroke. Currently available data suggest some pharmacokinetic and pharmacodynamic effects of aflibercept by explaining its pro-thrombotic profile.
Department of Pharmacy, Toulouse University Hospital, Toulouse, France.
J
J
Thorel
Department of Pharmacy, Toulouse University Hospital, Toulouse, France.
E
E
Civade
Department of Ophthalmology, Toulouse University Hospital, Toulouse, France.
J C
JC
Quintyn
Department of Pharmacy, Toulouse University Hospital, Toulouse, France.|Faculty of Pharmaceutical Sciences, Paul Sabatier University, Toulouse, France.
P
P
Cestac
Service de Pharmacologie Médicale et Clinique, Centre Midi-Pyrénées de PharmacoVigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, CHU de Toulouse, Université de Toulouse, INSERM U1027, Faculté de Médecine, Toulouse, France.
J-L
JL
Montastruc
Service de Pharmacologie Médicale et Clinique, Centre Midi-Pyrénées de PharmacoVigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, CHU de Toulouse, Université de Toulouse, INSERM U1027, Faculté de Médecine, Toulouse, France.
H
H
Bagheri
D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D004347:Drug Interactions; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000188:drug therapy; D000069579:Ranibizumab / Q000008:administration & dosage; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage* / Q000009:adverse effects; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D020521:Stroke / Q000209:etiology* / Q000473:pathology; D013997:Time Factors; D014812:Vitamin K / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D011993:Recombinant Fusion Proteins; D014812:Vitamin K; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab
anti-vascular endothelial growth factor agents; drug interactions; thrombosis