Effects of sildenafil on maximum walking time in patients with arterial claudication: The ARTERIOFIL study.
Aged
Biomarkers
/ blood
Cross-Over Studies
Double-Blind Method
Exercise Tolerance
/ drug effects
Female
France
Humans
Intermittent Claudication
/ blood
Male
Middle Aged
Peripheral Arterial Disease
/ blood
Phosphodiesterase 5 Inhibitors
/ adverse effects
Prospective Studies
Recovery of Function
Sildenafil Citrate
/ adverse effects
Time Factors
Treatment Outcome
Walk Test
Walking
Absolute walking time
Claudication
Exercise oximetry.
Peripheral artery disease
Sildenafil
Treadmill walking test
Journal
Vascular pharmacology
ISSN: 1879-3649
Titre abrégé: Vascul Pharmacol
Pays: United States
ID NLM: 101130615
Informations de publication
Date de publication:
Historique:
received:
09
03
2019
revised:
07
05
2019
accepted:
26
05
2019
pubmed:
4
6
2019
medline:
6
5
2020
entrez:
2
6
2019
Statut:
ppublish
Résumé
Patients with lower extremity peripheral artery disease (PAD) frequently experience claudication, a clinical symptom indicative of reduced walking capacity. Recommended care consists of exercise rehabilitation combined with optimal medical treatment and surgery. The effects of a single oral dose of sildenafil, a phosphodiesterase type-5 inhibitor, on patients with claudication are discussed. The aim of this study was to test the efficacy of a single 100 mg dose of sildenafil compared to placebo in terms of maximal walking time (MWT) in patients with claudication. The ARTERIOFIL study is a crossover, double-blind, prospective, randomized, single-center study conducted at Angers University Hospital in France. MWT (primary endpoint) was assessed using a treadmill test (10% incline; 3.2 km/h). Secondary endpoints (pain-free walking time (PFWT), transcutaneous oximetry during exercise and redox cycle parameters and safety) were also studied. Fourteen patients were included of whom two were ultimately excluded. In the 12 remaining patients, the MWT was significantly improved during the sildenafil period compared with the placebo period (300 s [95% CI 172 s-428 s] vs 402 s [95% CI 274 s-529 s] p < 0.01). Sildenafil had no significant effect on pain-free walking time or skin tissue oxygenation during exercise. According to redox cycle parameters, sildenafil significantly reduced blood glucose and pyruvate levels and the 3-hydroxybutyrate/acetoacetate ratio, while there was no significant effect on lactate, 3-hydroxybutyrate, acetoacetate and free fatty acid levels. Symptomatic transient hypotension was observed in two women. The ARTERIOFIL study has shown that a single 100 mg oral dose of sildenafil had a significant effect on increase in MWT but had no significant effects on PFWT and oxygenation parameters in patients with claudication. A double-blind, prospective, randomized, multicenter study (VIRTUOSE©) is ongoing to evaluate the chronic effect of six month-long sildenafil treatment on MWT in PAD patients with claudication. This clinical trial was registered at clinicaltrials.gov, registration. number: NCT02832570, (https://clinicaltrials.gov/ct2/show/NCT02832570).
Sections du résumé
BACKGROUND
Patients with lower extremity peripheral artery disease (PAD) frequently experience claudication, a clinical symptom indicative of reduced walking capacity. Recommended care consists of exercise rehabilitation combined with optimal medical treatment and surgery. The effects of a single oral dose of sildenafil, a phosphodiesterase type-5 inhibitor, on patients with claudication are discussed. The aim of this study was to test the efficacy of a single 100 mg dose of sildenafil compared to placebo in terms of maximal walking time (MWT) in patients with claudication.
METHODS
The ARTERIOFIL study is a crossover, double-blind, prospective, randomized, single-center study conducted at Angers University Hospital in France. MWT (primary endpoint) was assessed using a treadmill test (10% incline; 3.2 km/h). Secondary endpoints (pain-free walking time (PFWT), transcutaneous oximetry during exercise and redox cycle parameters and safety) were also studied.
RESULTS
Fourteen patients were included of whom two were ultimately excluded. In the 12 remaining patients, the MWT was significantly improved during the sildenafil period compared with the placebo period (300 s [95% CI 172 s-428 s] vs 402 s [95% CI 274 s-529 s] p < 0.01). Sildenafil had no significant effect on pain-free walking time or skin tissue oxygenation during exercise. According to redox cycle parameters, sildenafil significantly reduced blood glucose and pyruvate levels and the 3-hydroxybutyrate/acetoacetate ratio, while there was no significant effect on lactate, 3-hydroxybutyrate, acetoacetate and free fatty acid levels. Symptomatic transient hypotension was observed in two women.
CONCLUSIONS
The ARTERIOFIL study has shown that a single 100 mg oral dose of sildenafil had a significant effect on increase in MWT but had no significant effects on PFWT and oxygenation parameters in patients with claudication. A double-blind, prospective, randomized, multicenter study (VIRTUOSE©) is ongoing to evaluate the chronic effect of six month-long sildenafil treatment on MWT in PAD patients with claudication.
CLINICAL TRIAL REGISTRATION
This clinical trial was registered at clinicaltrials.gov, registration. number: NCT02832570, (https://clinicaltrials.gov/ct2/show/NCT02832570).
Identifiants
pubmed: 31152977
pii: S1537-1891(19)30080-1
doi: 10.1016/j.vph.2019.05.003
pii:
doi:
Substances chimiques
Biomarkers
0
Phosphodiesterase 5 Inhibitors
0
Sildenafil Citrate
BW9B0ZE037
Banques de données
ClinicalTrials.gov
['NCT02832570']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
106563Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.