Prasugrel as opposed to clopidogrel improves endothelial nitric oxide bioavailability and reduces platelet-leukocyte interaction in patients with unstable angina pectoris: A randomized controlled trial. (1st December 2017)

• Record Type: Journal Article
• Authors: Rudolph, Tanja K.; Fuchs, Alexander; Klinke, Anna; Schlichting, Andrea; Friedrichs, Kai; Hellmich, Martin; Mollenhauer, Martin; Schwedhelm, Edzard; Baldus, Stephan; Rudolph, Volker
• Is Part Of: International journal of cardiology. Volume 248(2017)
• Page Start: 7
• Page End: 13
• Publication Date: 2017-12-01
• Subjects: FMD flow-mediated dilation -- hsCRP high-sensitivity C-reactive protein -- MPO myeloperoxidase -- NO nitric oxide -- PLA platelet-leukocyte aggregates -- RANTES regulated on activation, normal T cell expressed and secreted -- sCD40L soluble CD40 ligand; Atherosclerosis -- Coronary artery disease -- Endothelial function -- Platelet-leukocyte interaction -- Inflammation -- Prasugrel; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2017.06.099
• Languages: English
• ISSNs: 0167-5273

Abstract

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 75 mg (n = 23) or prasugrel 10 mg (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 3 months. Results: Baseline patient demographics were well matched between treatment groups. Prasugrel led to a significant improvement of FMD after 3 months (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). Highlights: Prasugrel as opposed to clopidogrel improves endothelial function and nitric oxide bioavailability. More potent platelet inhibition results in lower platelet-derived inflammatory markers. Prasugrel reduces platelet-leukocyte aggregates.