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Published in: Clinical Research in Cardiology 2/2010

01-02-2010 | Original Paper

Effects of pentaerythritol tetranitrate on endothelial function in coronary artery disease: results of the PENTA study

Authors: Boris Schnorbus, Robert Schiewe, Mir Abolfazl Ostad, Christoph Medler, Daniel Wachtlin, Philip Wenzel, Andreas Daiber, Thomas Münzel, Ascan Warnholtz

Published in: Clinical Research in Cardiology | Issue 2/2010

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Abstract

Background

Pentaerythritol tetranitrate (PETN) differs from other organic nitrates by the lack of tolerance induction and by antioxidative properties. The purpose of this study was to determine the effect of PETN on endothelial function in patients with coronary artery disease (CAD). We hypothesized that the treatment with PETN improves endothelial function in patients with CAD.

Methods

In a prospective, double-blind study, we randomly assigned 80 patients to treatment for 8 weeks with oral PETN 80 mg t.i.d. (PETN) or placebo (C). The primary endpoint was the absolute change in brachial artery flow-mediated dilation (FMD) from baseline to follow-up. Furthermore, changes in nitroglycerin-mediated dilation (NMD), digital peripheral arterial tonometry (PAT) index, vascular shear stress, mean flow velocity, plasma bilirubin, C-reactive protein (CRP) and thiobarbituric acid reactive substances (TBARS), serum ferritin, and the activity of the PETN bioactivating enzyme aldehyde dehydrogenase-2 (ALDH-2) in peripheral blood mononuclear cells were analyzed. Raw data entry, data monitoring and statistical analysis were performed independently.

Results

The treatment groups were comparable regarding demographics, cardiovascular risk and concomitant medication. There was no difference in the change in FMD between the two treatment groups (mean ± SD: PETN: +1.6 ± 3.3% vs. C: +1.4 ± 4.1%; P = 0.7). NMD increased after treatment with PETN and was higher compared with C (PETN: +3.8 ± 5.5% vs. C: +0.6 ± 4.2%; P = 0.004). Mean PAT index and ALDH-2 activity remained unchanged. Relative changes in mean flow volume (P = 0.04) and mean flow velocity (P = 0.01) upon ischemia increased in the PETN group versus C. Changes in bilirubin, ferritin, TBARS and CRP did not differ between the groups.

Conclusions

We conclude that chronic PETN therapy in patients with CAD may be established for symptomatic treatment without adverse effects on endothelial function and with beneficial effects on the microcirculation.
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Metadata
Title
Effects of pentaerythritol tetranitrate on endothelial function in coronary artery disease: results of the PENTA study
Authors
Boris Schnorbus
Robert Schiewe
Mir Abolfazl Ostad
Christoph Medler
Daniel Wachtlin
Philip Wenzel
Andreas Daiber
Thomas Münzel
Ascan Warnholtz
Publication date
01-02-2010
Publisher
Springer-Verlag
Published in
Clinical Research in Cardiology / Issue 2/2010
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-009-0096-z

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