Novel therapeutic approaches in pulmonary arterial hypertension: focus on tadalafil

Pulmonary arterial hypertension (PAH) is an enigmatic, often fatal disease of the lung. Excess vasoconstriction and progressive obliteration of the precapillary arterioles combine to reduce the cross-sectional area for blood flow and thus cause chronic elevation in the pulmonary arterial pressures with progressive right heart dysfunction, heart failure and death. In 1995, the FDA approved the first therapy for PAH: epoprostenol, a highly efficacious drug but one that was difficult to use for patients and clinicians alike. Since then, there have been eight additional drugs approved, each offering advantages in terms of convenience over previously available drugs. In 2009, tadalafil (Adcirca®) was approved for PAH. The 405 patients enrolled in the single pivotal trial give this drug the largest initial placebo-controlled dataset of any of the oral PAH therapies; its once-daily dosing and excellent safety profile make it the most convenient of the therapies by a significant margin. After introducing the PAH disease state with references for more interested readers, this paper discusses the nitric oxide pathway as it relates to the pulmonary circulation, provides an overview of clinically available phosphodiesterase inhibitors and discusses tadalafil in relationship to sildenafil (Revatio®), the first phosphodiesterase inhibitor approved for PAH.