Back to Search
Start Over
Dual pathway inhibition as compared to acetylsalicylic acid monotherapy in relation to endothelial function in peripheral artery disease, a phase IV clinical trial
- Source :
- Frontiers in Cardiovascular Medicine, 9:979819. Frontiers Research Foundation, Frontiers in Cardiovascular Medicine, 9, Frontiers in cardiovascular medicine, 9:979819. Frontiers Media S.A.
- Publication Year :
- 2022
-
Abstract
- ObjectiveDual pathway inhibition (DPI) by combining acetylsalicylic acid (ASA) with low-dose rivaroxaban has been shown to reduce cardiovascular events in patients with peripheral arterial disease (PAD) when compared to ASA monotherapy. A potential explanation is that inhibition of factor Xa improves endothelial function through crosstalk between coagulation and inflammatory pathways, subsequently attenuating the occurrence of cardiovascular events. We hypothesize that the addition of rivaroxaban to ASA in PAD patients leads to improved endothelial function.DesignAn investigator-initiated, multicentre trial investigating the effect of DPI on endothelial function.MethodsPatients, diagnosed with PAD, were enrolled in two cohorts: cohort A (Rutherford I-III) and cohort B (Rutherford IV-VI). Participants received ASA monotherapy for a 4-weeks run-in period, followed by 12 weeks of DPI. Macro- and microvascular endothelial dysfunction were studied by measuring carotid artery reactivity upon sympathetic stimulus and by measuring plasma endothelin-1 concentrations, respectively. All measurements were performed during the use of ASA (baseline) and after 12 weeks of DPI.Results159 PAD patients (111 cohort A, 48 cohort B) were enrolled. Twenty patients discontinued study drugs early. Carotid artery constriction upon sympathetic stimulation at baseline (ASA) and after 12 weeks of DPI was similar in the total group, 22.0 vs. 22.7% (p = 1.000), and in the subgroups (Cohort A 22.6 vs. 23.7%, p = 1.000; cohort B 20.5 vs. 20.5%, p = 1.000), respectively. The mean concentration of plasma endothelin-1 at baseline and after 12 weeks of DPI did not differ, 1.70 ± 0.5 vs. 1.66 ± 0.64 pmol/L (p = 0.440) in the total group, 1.69 ± 0.59 vs. 1.62 ± 0.55 pmol/L in cohort A (p = 0.202), and 1.73 ± 0.53 vs. 1.77 ± 0.82 pmol/L in cohort B (p = 0.682), respectively.ConclusionMacro- and microvascular endothelial dysfunction, as reflected by carotid artery reactivity and plasma endothelin-1 concentrations, are not influenced in PAD patients by addition of low-dose rivaroxaban to ASA monotherapy for 12 weeks.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04218656.
- Subjects :
- RISK
aspirin
Other Research Radboud Institute for Health Sciences [Radboudumc 0]
Vascular damage Radboud Institute for Health Sciences [Radboudumc 16]
Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16]
FLOW-MEDIATED DILATION
factor Xa inhibitors
RELAXATION
CARDIOVASCULAR EVENT RATES
DYSFUNCTION
endothelial cells
ACTIVATION
All institutes and research themes of the Radboud University Medical Center
peripheral arterial disease
ORAL ANTICOAGULANT
Renal disorders Radboud Institute for Health Sciences [Radboudumc 11]
FACTOR XA
OUTPATIENTS
Cardiology and Cardiovascular Medicine
rivaroxaban
vascular endothelium
Subjects
Details
- Language :
- English
- ISSN :
- 2297055X
- Database :
- OpenAIRE
- Journal :
- Frontiers in Cardiovascular Medicine, 9:979819. Frontiers Research Foundation, Frontiers in Cardiovascular Medicine, 9, Frontiers in cardiovascular medicine, 9:979819. Frontiers Media S.A.
- Accession number :
- edsair.doi.dedup.....688910caded2192d6db3bbc71a225406