Efficacy of the long-acting nitro vasodilator pentaerithrityl tetranitrate in patients with chronic stable angina pectoris receiving anti-anginal background therapy with beta-blockers: a 12-week, randomized, double-blind, placebo-controlled trial.
BACKGROUND
The organic nitrate pentaerithrityl tetranitrate (PETN) has been shown to have ancillary properties that prevent the development of tolerance and endothelial dysfunction. This randomized, double-blind, placebo-controlled, multicentre study ('CLEOPATRA' study) was designed to investigate the anti-ischaemic efficacy of PETN 80 mg b.i.d. (morning and mid-day) over placebo in patients with chronic stable angina pectoris.


RESULTS
A total of 655 patients were evaluated in the intention-to-treat population, randomized to PETN (80 mg b.i.d., n = 328) or placebo (n = 327) and completed the study. Patients underwent treadmill exercise tests at randomization, after 6 and 12 weeks of treatment. Treatment with PETN over 12 weeks did not modify the primary endpoint total exercise duration (TED, P = 0.423). In a pre-specified sub-analysis of patients with reduced exercise capacity (TED at baseline ≤9 min, n = 257), PETN appeared more effective than placebo treatment (P = 0.054). Superiority of PETN over placebo was evident in patients who were symptomatic at low exercise levels (n = 120; P = 0.017). Pentaerithrityl tetranitrate 80 mg b.i.d. was well tolerated, and the overall safety profile was comparable with placebo.


CONCLUSIONS
Although providing no additional benefit in unselected patients with known coronary artery disease, PETN therapy, administered in addition to modern anti-ischaemic therapy, could increase exercise tolerance in symptomatic patients with reduced exercise capacity.
2. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, University Medical Center Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
Thomas
T
Münzel
Thomas
T
Meinertz
Ulrich
U
Tebbe
Heinrich Theodor
HT
Schneider
Dirk
D
Stalleicken
Manfred
M
Wargenau
Tommaso
T
Gori
Ingrid
I
Klingmann
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000627:therapeutic use; D060050:Angina, Stable / Q000188:drug therapy*; D002908:Chronic Disease; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D010417:Pentaerythritol Tetranitrate / Q000008:administration & dosage*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage*
D000319:Adrenergic beta-Antagonists; D003692:Delayed-Action Preparations; D014665:Vasodilator Agents; D010417:Pentaerythritol Tetranitrate
Chronic stable angina; Organic nitrate; Pentaerithrityl tetranitrate; Total exercise duration