Source: DGNews  |  Posted 3 years ago

By Em Brown

PHILADELPHIA -- November 1, 2008 -- Tadalafil, a phosphodiesterase type 5 inhibitor, shows "clear durability of effect" in the treatment of pulmonary arterial hypertension (PAH), researchers reported here at CHEST 2008, the annual meeting of the American College of Chest Physicians.

Results of a phase 3 study presented here on October 28 also demonstrated safety and tolerability with tadalafil.

The 16-week, double-blind, placebo-controlled study involved 405 patients with idiopathic PAH or PAH associated with connective-tissue disease, anorexigen use, HIV, atrial septal defect, or surgical repair of congenital left-to-right shunt.

The study was led by Robyn J. Barst, MD, Columbia University College of Physicians and Surgeons, Columbia University Medical Center, and New York-Presbyterian Hospital/Weill Cornell Medical Center, Pulmonary Hypertension Center, New York, New York.

Patients were randomised to placebo or tadalafil 2.5, 10, 20, or 40 mg orally once daily. Treatment was given as monotherapy or as add-on therapy to bosentan (in 53% of patients) for 16 weeks.

Tadalafil 40 mg increased the 6-minute-walk-distance (6MWD) by 41.1 minutes compared with an increase of 9.2 minutes over baseline with placebo (P < .001). Among the 189 patients not taking concomitant bosentan therapy, patients on tadalafil 40 mg had an increase of 42.2 minutes in 6MWD compared with an increase of 2.9 minutes for patients on placebo (P < .01).

Tadalafil 40 mg delayed the time to clinical worsening compared with placebo, with a relative risk reduction of 68% less than placebo (P < .05).

Improvements were observed in 6 of 8 Short Form-36 health-survey domains among patients randomised to tadalafil 40 mg (P < .001), the visual analogue scale (VAS, P < .05), and the Euro-Quality of Life US and UK scores (both P < .05).

Tadalafil 40 mg increased cardiac output by 0.6 L/min, reduced pulmonary-artery pressure by 4.3 mm Hg, and decreased pulmonary vascular resistance by 209 dyn.s/cm5 compared with baseline (P < .05).

The most common treatment-related adverse event reported with tadalafil was headache (32% tadalafil patients vs 15% patients).

Changes in World Health Organization functional class and Borg dyspnoea score did not differ significantly compared with placebo.

"[These are] preliminary data, it's just a snapshot, but it is consistent with findings of this class of drugs in the treatment of PAH," commented Lewis J. Rubin, MD, chairman of the American College of Chest Physicians' Task Force on Treatment Guidelines for PAH.

"These findings are positive overall and show clear durability of effect," Dr. Rubin noted.

Funding for this study was provided by Eli Lilly and Company.

[Presentation title: Tadalafil Improves Exercise Capacity, Health Related Quality of Life and Delays Time to Clinical Worsening in Patients With Symptomatic Pulmonary Arterial Hypertension (PAH). Abstract AS2244]