Tanja K Rudolph1, Alexander Fuchs2, Anna Klinke2, Andrea Schlichting3, Kai Friedrichs2, Martin Hellmich4, Martin Mollenhauer2, Edzard Schwedhelm5, Stephan Baldus2, Volker Rudolph2. 1. University of Cologne, Heart Center, Department of Cardiology, Cologne Cardiovascular Research Center, Cologne, Germany. Electronic address: tanja.rudolph@uk-koeln.de. 2. University of Cologne, Heart Center, Department of Cardiology, Cologne Cardiovascular Research Center, Cologne, Germany. 3. University of Hamburg, Heart Center, Department of Cardiology - Electrophysiology, Hamburg, Germany. 4. Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany. 5. Department of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Abstract
BACKGROUND: Platelet inhibition has been linked to improved endothelial function, a prognostic factor in coronary artery disease. Whether prasugrel, a potent platelet inhibitor, affects endothelial function remains unknown. METHODS: This was a double-blind, randomized, active-controlled, parallel trial. Patients with unstable angina pectoris undergoing percutaneous coronary intervention (PCI) received either a daily dose of clopidogrel 75mg (n=23) or prasugrel 10mg (n=22). Flow-mediated dilation (FMD), circulating nitrate and nitrite, inflammatory markers and platelet-leukocyte aggregates (PLAs) were assessed the day after PCI and after 3months. RESULTS: Baseline patient demographics were well matched between treatment groups. Prasugrel led to a significant improvement of FMD after 3months (9.01±3.64% vs. 6.65±3.24%, p=0.001). In contrast, no significant change was observed in the clopidogrel group (7.21±2.84% vs. 6.30±2.97%, p=0.187). Adjusted for baseline FMD, hyperlipidemia and statin use, the treatment effect on change in FMD favoured prasugrel by an absolute 1.97% (95% CI 0.29% to 3.66%, p=0.023). A significant reduction of plasma hsCRP, myeloperoxidase and neutrophil elastase and an increase of nitrate levels were noted in both treatment arms. Interestingly, only prasugrel significantly reduced sCD40 ligand and RANTES and increased nitrite levels. Prasugrel reduced the ADP-stimulated increase in PLAs by 40% (IR: 82 to 13), whereas clopidogrel revealed no such effect (1% increase (IR: 13 to 50) (p=0.01). CONCLUSION:Prasugrel exhibits beneficial mid-term effects on endothelial nitric oxide bioavailability and inflammatory markers. (EudraCT number: 2009-015406-19).
RCT Entities:
BACKGROUND: Platelet inhibition has been linked to improved endothelial function, a prognostic factor in coronary artery disease. Whether prasugrel, a potent platelet inhibitor, affects endothelial function remains unknown. METHODS: This was a double-blind, randomized, active-controlled, parallel trial. Patients with unstable angina pectoris undergoing percutaneous coronary intervention (PCI) received either a daily dose of clopidogrel 75mg (n=23) or prasugrel 10mg (n=22). Flow-mediated dilation (FMD), circulating nitrate and nitrite, inflammatory markers and platelet-leukocyte aggregates (PLAs) were assessed the day after PCI and after 3months. RESULTS: Baseline patient demographics were well matched between treatment groups. Prasugrel led to a significant improvement of FMD after 3months (9.01±3.64% vs. 6.65±3.24%, p=0.001). In contrast, no significant change was observed in the clopidogrel group (7.21±2.84% vs. 6.30±2.97%, p=0.187). Adjusted for baseline FMD, hyperlipidemia and statin use, the treatment effect on change in FMD favoured prasugrel by an absolute 1.97% (95% CI 0.29% to 3.66%, p=0.023). A significant reduction of plasma hsCRP, myeloperoxidase and neutrophil elastase and an increase of nitrate levels were noted in both treatment arms. Interestingly, only prasugrel significantly reduced sCD40 ligand and RANTES and increased nitrite levels. Prasugrel reduced the ADP-stimulated increase in PLAs by 40% (IR: 82 to 13), whereas clopidogrel revealed no such effect (1% increase (IR: 13 to 50) (p=0.01). CONCLUSION:Prasugrel exhibits beneficial mid-term effects on endothelial nitric oxide bioavailability and inflammatory markers. (EudraCT number: 2009-015406-19).
Authors: Kinga Pluta; Kinga Porębska; Tomasz Urbanowicz; Aleksandra Gąsecka; Anna Olasińska-Wiśniewska; Radosław Targoński; Aleksandra Krasińska; Krzysztof J Filipiak; Marek Jemielity; Zbigniew Krasiński Journal: Biology (Basel) Date: 2022-01-30
Authors: Riobaldo M R Cintra; Alexandre A S Soares; Ikaro Breder; Daniel B Munhoz; Joaquim Barreto; Sheila T Kimura-Medorima; Pamela Cavalcante; Renata Zanchetta; Jessica Cunha Breder; Camila Moreira; Vitor W Virginio; Isabella Bonilha; Jose Carlos Lima-Junior; Otavio R Coelho-Filho; Vaneza L W Wolf; Gil Guerra-Junior; Daniela C Oliveira; Rodrigo Haeitmann; Vicente H R Fernandes; Wilson Nadruz; Fernando R P Chaves; Carlos E L Arieta; Thiago Quinaglia; Andrei C Sposito Journal: Diabetol Metab Syndr Date: 2019-07-31 Impact factor: 3.320