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

Abstract

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. The purpose of this review is to evaluate the existing evidence for the use of tadalafil, a selective phosphodiesterase type 5 inhibitor, in PAH. 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. 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.