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Efficacy of the Long-Acting Nitro Vasodilator Pentaerithyrityl 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
Study Questions:
What is the anti-ischemic efficacy of pentaerithrityl tetranitrate (PETN), compared to placebo, in patients with chronic stable angina pectoris on background anti-ischemic therapy?
Methods:
CLEOPATRA was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients had a history of stable effort angina >3 months prior to study entry with at least four angina pectoris attacks in the 4-week period preceding randomization. Patients were randomized to PETN 80 mg twice daily or placebo and underwent treadmill stress testing at randomization and after 6 and 12 weeks of treatment. The primary efficacy endpoint was the total exercise duration (TED) after 12 weeks of treatment.
Results:
A total of 655 patients were evaluated in the intention-to-treat population; 87.8% of the intention-to-treat population was using background anti-anginal therapy with beta-blocker or ivabradine. There was no difference in TED between the two treatment groups (p = 0.423). In a prespecified analysis of patients with reduced exercise capacity (TED at baseline ≤9 minutes), PETN was more effective than placebo in improving TED (difference between PETN and placebo with regard to change in TED after 12 weeks of treatment was 31.9 seconds, range -0.6 to 64.4, p = 0.054). The overall safety profile of PETN was comparable to that of placebo.
Conclusions:
Treatment with PETN was no more effective than placebo in improving total exercise duration following 12 weeks of therapy. However, therapy was modestly more effective in selected patients with coronary artery disease and reduced exercise tolerance at baseline.
Perspective:
PETN is an organic nitrate that is not limited by the induction of tolerance and endothelial dysfunction, side effects that may limit the benefits of conventional nitrate therapy. Although these characteristics may make organic nitrate therapy appealing, the current analysis suggests that the modest benefits of PETN are limited to those patients with reduced exercise capacity at baseline. Accordingly, the role of PETN seems limited, particularly in unselected patients with coronary artery disease.
Keywords: Benzazepines, Pentaerythritol Tetranitrate, Exercise Test
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