Effects of pentaerythritol tetranitrate on endothelial function in coronary artery disease: results of the PENTA study.
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.
Schnorbus
Boris
B
Department of Medicine II, Mainz University Medical Center, Langenbeckstrasse 1, 55101 Mainz, Germany.
Schiewe
Robert
R
Ostad
Mir Abolfazl
MA
Medler
Christoph
C
Wachtlin
Daniel
D
Wenzel
Philip
P
Daiber
Andreas
A
Münzel
Thomas
T
Warnholtz
Ascan
A
D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000188:drug therapy*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010417:Pentaerythritol Tetranitrate / Q000008:administration & dosage*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage
D014665:Vasodilator Agents; D010417:Pentaerythritol Tetranitrate