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Clinical Trial
. 2021 May 5;77(5):1591-1599.
doi: 10.1161/HYPERTENSIONAHA.120.16454. Epub 2021 Mar 29.

Mechanisms Underlying Vascular Endothelial Growth Factor Receptor Inhibition-Induced Hypertension: The HYPAZ Trial

Kaisa M Mäki-Petäjä #  1 , Adam McGeoch #  1 , Lucy L Yang  1 , Annette Hubsch  1 , Carmel M McEniery  1 , Paul A R Meyer  1   2 , Fraz Mir  1 , Parag Gajendragadkar  1 , Nicola Ramenatte  3 , Gayathri Anandappa  4 , Sara Santos Franco  5 , Simon J Bond  3 , Carola-Bibiane Schönlieb  6 , Yoeri Boink  7   8 , Christoph Brune  7 , Ian B Wilkinson  1   3 , Duncan I Jodrell  4   3 , Joseph Cheriyan  1   3
Affiliations
Clinical Trial

Mechanisms Underlying Vascular Endothelial Growth Factor Receptor Inhibition-Induced Hypertension: The HYPAZ Trial

Kaisa M Mäki-Petäjä et al. Hypertension. .

Abstract

[Figure: see text].

Trial registration: ClinicalTrials.gov NCT01392352.

Keywords: acetylcholine; cardiovascular disease; hypertension; microvascular rarefaction; pazopanib.

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Conflict of interest statement

Disclosures

JC is a full time employee of Cambridge University Hospitals NHS Foundation Trust, but was seconded by the Trust for 50% of his NHS salaried time to work on GSK clinical trials until 2020. He received no employee benefits or shares/dividends or income from GSK. SSF is an employee of GSK and has received personal fees and other benefits from GSK outside the submitted work. Novartis Europharm Limited (Dublin, Ireland) is the current marketing authorisation holder of pazopanib (Votrient®) and has reviewed this manuscript. Other authors declare no conflicts.

Figures

Figure 1
Figure 1. Change in the forearm blood flow ratio (infused/ control arm)
FBF responses to Acetylcholine (panel A), Sodium nitroprusside (panel B), and NG-monomethyl-L-arginine (panel C) at baseline (blue line), at 2 weeks after initiation of pazopanib (red line) and at 12 weeks (green line) or when subject became hypertensive (Visit HYP). * denotes P<0.001 (a hierarchical mixed effects model). Data are expressed as a geometric mean FBF ratio (infused to control arm) ± SEM.
Figure 2
Figure 2. Haemoglobin imaging
Panel A) Representative images from the conjunctival and episcleral haemoglobin video imaging (1 pixel equals 10μm2). One-minute videos were recorded using a modified slit lamp. The videos were aligned and overlaid to yield a single image, which was segmented and stratified according the vessel diameter using a pre-trained U-Net convolutional neural network. The stratification is represented by the different colours in the images shown. Panel B) Microvascular density (blue) and diameter (orange) at baseline and at two weeks after initiation of treatment. Data are expressed as a mean ± SEM. * denotes P<0.05.
Figure 3
Figure 3. Percentage inhibition of acetylcholine esterase (AChE) activity
AChE activity was assessed in whole blood samples taken from 10 healthy volunteers and spiked in a range of concentration of pazopanib. ANOVA P<0.001. Data are expressed as a mean ± SEM.
See this image and copyright information in PMC

References

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