Prasugrel as opposed to clopidogrel improves endothelial function in patients with unstable angina: A randomized controlled trial

 2017 Jul 1. pii: S0167-5273(16)34288-7. doi: 10.1016/j.ijcard.2017.06.099. [Epub ahead of print]

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.

Rudolph TK1, Fuchs A2, Klinke A2, Schlichting A3, Friedrichs K2, Hellmich M4, Mollenhauer M2, Schwedhelm E5, Baldus S2, Rudolph V2.

Author information

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).

KEYWORDS:

Atherosclerosis; Coronary artery disease; Endothelial function; Inflammation; Platelet-leukocyte interaction; Prasugrel

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