Effect of sildenafil on maternal hemodynamics in pregnancies complicated by severe early-onset fetal growth restriction: planned subgroup analysis from a multicenter randomized placebo-controlled double-blind trial.
Adult
Blood Pressure
/ drug effects
Double-Blind Method
Female
Fetal Growth Retardation
/ drug therapy
Heart Rate
/ drug effects
Hemodynamics
/ drug effects
Humans
Phosphodiesterase 5 Inhibitors
/ administration & dosage
Placental Circulation
/ drug effects
Pregnancy
Pregnancy Complications, Cardiovascular
/ drug therapy
Pulse Wave Analysis
Sildenafil Citrate
/ administration & dosage
Stroke Volume
/ drug effects
Treatment Outcome
Ultrasonography, Prenatal
Umbilical Arteries
/ physiopathology
Vascular Stiffness
/ drug effects
cardiovascular
endothelium
fetal growth restriction
hemodynamics
nitric oxide
pharmacology
sildenafil
vascular biology
Journal
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology
ISSN: 1469-0705
Titre abrégé: Ultrasound Obstet Gynecol
Pays: England
ID NLM: 9108340
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
10
03
2019
revised:
07
07
2019
accepted:
09
08
2019
pubmed:
23
8
2019
medline:
25
11
2021
entrez:
22
8
2019
Statut:
ppublish
Résumé
Fetal growth restriction (FGR) is associated with maternal cardiovascular changes. Sildenafil, a phosphodiesterase type-5 inhibitor, potentiates the actions of nitric oxide, and it has been suggested that it alters maternal hemodynamics, potentially improving placental perfusion. Recently, the Dutch STRIDER trial was stopped prematurely owing to excess neonatal mortality secondary to pulmonary hypertension. The main aim of this study was to investigate the effect of sildenafil on maternal hemodynamics in pregnancies with severe early-onset FGR. This was a cardiovascular substudy within a UK multicenter, placebo-controlled trial, in which 135 women with a singleton pregnancy and severe early-onset FGR (defined as a combination of estimated fetal weight or abdominal circumference below the 10 Included were 134 women assigned randomly to sildenafil (n = 69) or placebo (n = 65) who had maternal BP and HR recorded at baseline. At 1-2 h post-randomization, compared with baseline values, sildenafil increased maternal HR by 4 bpm more than did placebo (mean difference, 5.00 bpm (95% CI, 1.00-12.00 bpm) vs 1.25 bpm (95% CI, -5.38 to 7.88 bpm); P = 0.004) and reduced systolic BP by 1 mmHg more (mean difference, -4.13 mmHg (95% CI, -9.94 to 1.44 mmHg) vs -2.75 mmHg (95% CI, -7.50 to 5.25 mmHg); P = 0.048). Even after adjusting for maternal mean arterial pressure, sildenafil reduced aortic PWV by 0.60 m/s more than did placebo (mean difference, -0.90 m/s (95% CI, -1.31 to -0.51 m/s) vs -0.26 m/s (95% CI, -0.75 to 0.59 m/s); P = 0.001). Sildenafil was associated with a non-significantly greater decrease in SV index after 1-2 h post-randomization than was placebo (mean difference, -5.50 mL/m Sildenafil in a dose of 25 mg three times daily increases HR, reduces BP and reduces arterial stiffness in pregnancies complicated by severe early-onset FGR. These changes are short term, modest and consistent with the anticipated vasodilatory effect. They have no short- or long-term clinical impact on the mother. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Substances chimiques
Phosphodiesterase 5 Inhibitors
0
Sildenafil Citrate
BW9B0ZE037
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
198-209Subventions
Organisme : Department of Health
ID : 12/62/109
Pays : United Kingdom
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : Efficacy and Mechanism Evaluation Programme
Informations de copyright
Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
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