Tadalafil: the evidence for its clinical potential in the treatment of pulmonary arterial hypertension

Abstract

Introduction:Pulmonary arterial hypertension (PAH), characterized by increased pulmonary artery pressures in the absence of elevated pulmonary venous pressures, is a progressive disease associated with reduced exercise capacity and increased mortality risk. Current treatments for PAH include nonspecific vasodilators, prostacyclin and related analogs, and endothelin receptor antagonists. Since phosphodiesterase type 5 is highly expressed in pulmonary vascular tissues, agents that selectively inhibit phosphodiesterase type 5 activity induce pulmonary arterial vasodilatation, and are being developed for the treatment of PAH.Aims:The purpose of this review is to evaluate the existing evidence for the use of tadalafil, a selective phosphodiesterase type 5 inhibitor, in PAH.Evidence review:Data from erectile dysfunction populations indicate that tadalafil is well tolerated with an elimination half-life of 17.5 hours. Small pilot studies in patients with PAH of mixed etiology demonstrate that tadalafil reduces pulmonary vascular resistance and is associated with improved clinical status. A multicenter, randomized, placebo-controlled clinical trial in patients with PAH is currently recruiting patients.Clinical potential:Based on existing studies of sildenafil, a related selective phosphodiesterase type 5 inhibitor in PAH, and the findings of initial pilot studies, tadalafil appears to have excellent potential to provide therapeutic benefit in patients with pulmonary hypertension. The long elimination half-life of tadalafil makes it suitable for once-daily dosing.

Tadalafil as monotherapy and in combination regimens for the treatment of pulmonary arterial hypertension

“…The exercise and functional capacity can be assessed using cardiopulmonary exercise testing or 6-min walk distance (6MWD) tests [Arif and Poon, 2011]. A mPAP ≥25 mmHg at rest or >30 mmHg with exercise and/or a pulmonary capillary wedge pressure (PCWP) of ≤15 mmHg (without the presence of mitral stenosis) and a mean PVR of ≥2 or 3 Wood units confirm the diagnosis of PAH [Arif and Poon, 2011;Barst et al 2011;Buckley et al 2010;Chin and Rubin, 2008;Falk et al 2010;Frey and Lang, 2012;Katz, 2008;Liang et al 2012;Naeije and Huez, 2007;Sanchez et al 2010].…”

“…The condition eventually leads to right-sided heart failure and death. The mean survival period is 2.8 years after the establishment of the diagnosis without treatment [Arif and Poon, 2011; Frey and Lang, 2012; Katz, 2008; Liang et al . 2012; Naeije and Huez, 2007; Sanchez et al .…”

“…2010; Chin and Rubin, 2008; Falk et al . 2010; Frey and Lang, 2012; Katz, 2008; Liang et al . 2012; Naeije and Huez, 2007; Sanchez et al .…”