title: Intensified monitoring of circadian blood pressure and heart rate before and after intravitreous injection of bevacizumab: preliminary findings of a pilot study.
abstract: BACKGROUND
  A dose-dependent increase in arterial blood pressure (BP) was seen during bevacizumab treatment given intravenously for metastatic carcinoma. Because low systemic levels can also be expected after the intravitreal administration of bevacizumab, we looked for possible haemodynamic reactions of patients at higher risk of developing cardiovascular events after bevacizumab injection.
  
  
  METHODS
  Ambulatory BP was monitored in 14 hypertensive patients receiving 1.25 mg intraocular bevacizumab for either choroidal neovascularization (CNV) or retinal proliferation associated with central retinal vein occlusion (CRVO). Circadian measurement was carried out twice, first at least 24 h prior to injection and second 72 h afterwards. Baseline evaluation before injection was compared with values taken in a matched control group. Taking a small random sample of two patients, serum concentration of bevacizumab and VEGF-A was measured at several time points.
  
  
  RESULTS
  High incidence of pathologic BP values was found in the pre-injection measurement, even under anti-hypertensive treatment of the patients with CNV or CRVO. No general increase in BP was seen after the intravitreal injection (P = 0.01), although significantly reduced nocturnal dipping occurred as compared to before the injection (P = 0.006). Individual patients showed a rise in BP load subsequent to injection. A decline in serum VEGF-A was found to correspond to measureable levels of serum bevacizumab (up to 90 ng/ml).
  
  
  CONCLUSIONS
  Before the intravitreal injection, BP values were increased in the majority of the patients. The elevated BP load might be related to probable pre-injection stressors. There seems to be no general rise in mean BP, heart rate and pulse pressure after intravitreal bevacizumab, although a decrease in serum VEGF-A can occur in individual patients. The reduced nocturnal dipping could be caused by pharmacodynamic effects on the vasal tone; this preliminary but striking finding warrants further investigation.
authors.affiliation: Center for Ophthalmology, Eberhard-Karls University of Tuebingen, Schleichstrasse 12, Tuebingen, Germany. Focke.Ziemssen@med.uni-tuebingen.de
authors.forename: Focke
authors.initials: F
authors.lastname: Ziemssen
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhu
authors.forename: Swaantje
authors.initials: S
authors.lastname: Peters
authors.forename: Salvatore
authors.initials: S
authors.lastname: Grisanti
authors.forename: Mohammed
authors.initials: M
authors.lastname: El Wardani
authors.forename: Peter
authors.initials: P
authors.lastname: Szurman
authors.forename: Karl U
authors.initials: KU
authors.lastname: Bartz-Schmidt
authors.forename: Tjalf
authors.initials: T
authors.lastname: Ziemssen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001794:Blood Pressure / Q000187:drug effects*; D001795:Blood Pressure Determination; D020256:Choroidal Neovascularization / Q000150:complications / Q000188:drug therapy*; D002940:Circadian Rhythm; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000503:physiopathology; D007267:Injections; D008875:Middle Aged; D010865:Pilot Projects; D012160:Retina / Q000187:drug effects / Q000473:pathology; D012170:Retinal Vein Occlusion / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000097:blood; D014822:Vitreous Body
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab