Acute Hemodynamic Changes after Single Administration of Udenafil in Pulmonary Arterial Hypertension: a Phase IIa Study

Abstract

Background and objectives: Udenafil, a new phosphodiesterase-5 inhibitor (PDE5i), has been used to treat erectile dysfunction. Given the proven benefit of PDE5i in pulmonary arterial hypertension (PAH), we evaluated serial hemodynamic changes after single udenafil administration to determine the appropriate therapeutic dose.

Methods: Eighteen patients were randomly allocated into one of 3 groups: placebo, udenafil 50 mg (U50), and udenafil 100 mg (U100). Diagnosis for inclusion was idiopathic PAH or PAH associated with connective tissue disease. Patients with any contraindication to PDE5i, and/or PDE5i treatment in the past 1 month were excluded. Continuous hemodynamic monitoring was performed by placing a Swan-Ganz catheter. Information on cardiac index (CI), mean pulmonary arterial pressure (mPAP), mean systemic arterial pressure (mSAP), pulmonary arterial wedge pressure (PAWP), and pulmonary vascular resistance index (PVRI) was obtained for 4 hours after drug administration.

Results: The mPAP significantly decreased in both the U50 and U100 (-11 mmHg and -8 mmHg from baseline, respectively, p<0.1). The mSAP also decreased in both U50 and U100; however, the decrease was greater in the U100 (Δ=-8.5 mmHg and Δ=-14.0 mmHg). CI increased in the U50, but decreased in the U100. Although PVRI decreased in both, statistical significance was only achieved in the U50 compared to placebo. PAWP was stable during monitoring. U50 had at least 4 hour-effect after administration. Only 2 patients with U100 experienced mild adverse events.

Conclusions: This is the first demonstration of the acute hemodynamic changes induced by udenafil. U50 is considered an optimal dose for treating PAH with more than 4-hour treatment effect.

Trial registration: ClinicalTrials.gov Identifier: NCT01553721.

Keywords: Hemodynamic monitoring; Hypertension, Pulmonary; Phosphodiesterase 5 inhibitors.

Conflict of interest statement

This study was supported by Dong-A ST, but the sponsor had no role in the design of the study, the collection, and analysis of the data, or the preparation of the manuscript. The authors have no financial conflicts of interest.

Copyright © 2019. The Korean Society of Cardiology.

Figures

Figure 1. Changes in major hemodynamic parameters according to time. (A) Change in mPAP from baseline. (B) Change in PVRI from baseline. (C) Change in mSAP from baseline. (D) Change in CI from baseline.

CI = cardiac index; mPAP = mean pulmonary arterial pressure; mSAP = mean systemic arterial pressure; PVRI = pulmonary vascular resistance index; U50 = udenafil 50 mg; U100 = udenafil 100 mg.

Figure 2. Plotting of maximal PVRI change in udenafil on data from previous study by Ghofrani et al. Although plotted on different study subsets, change in maximal PVRI was greatest with U50, suggesting the highest selectivity of udenafil for pulmonary circulation, although udenafil is similar to sildenafil in molecular structure and is comparable in terms of PDE5 selectivity.

PDE5 = phosphodiesterase-5; PVRI = pulmonary vascular resistance index; U50 = udenafil 50 mg; U100 = udenafil 100 mg.