Abstract: Poster Presentations |


Ronald J. Oudiz, PhD*; Carl Arneson, MS; Michael Wade, PhD
Author and Funding Information

LA Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA


Chest. 2009;136(4_MeetingAbstracts):55S. doi:10.1378/chest.136.4_MeetingAbstracts.55S-b
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PURPOSE:  Tadalafil, a competitive inhibitor of phosphodiesterase 5, improved exercise capacity and had an acceptable safety profile in patients with pulmonary arterial hypertension (PAH) in a 16-week, phase 3 double-blind, placebo-controlled trial (PHIRST-1 study). In the long-term extension study (PHIRST-2), the six-minute walk distance (6MWD) was maintained over the 52-week period. We report clinical worsening for subjects remaining on tadalafil 20-mg or tadalafil 40-mg for entire 68-week treatment period across the 2 studies.

METHODS:  Across both studies there were 82 patients on 20-mg tadalafil and 79 patients on the 40-mg dose. Clinical worsening was defined as death, lung transplantation, atrial septostomy, new chronic treatment for PAH, worsening of WHO functional class or hospitalization due to worsening of PAH.

RESULTS:  In the initial 16-week study, there was a significant delay in clinical worsening for the patients in the 40-mg tadalafil group compared to placebo (p = 0.038; relative risk reduction 68%). Over the 52-week extension period, fewer subjects experienced clinical worsening with tadalafil 40-mg (n = 13, 16%) than with 20-mg (n = 15, 18%). Over both studies, numerically fewer subjects experienced clinical worsening with tadalafil 40-mg (n = 17, 22%) than with 20-mg (n = 23, 28%). In addition, fewer subjects who remained on tadalafil 40-mg across both studies (9%) compared to those who remained on tadalafil 20-mg across both studies (19%) experienced worsening WHO functional class. This observation was more pronounced in those subjects not taking concomitant bosentan, with 6% worsening on tadalafil 40-mg compared to 31% on tadalafil 20-mg.

CONCLUSION:  During the entire 68-week treatment, the probability of remaining free of clinical worsening tended to be greatest in the tadalafil 40-mg treatment group. A smaller proportion of patients taking the 40-mg dose experienced a decline in WHO functional class.

CLINICAL IMPLICATIONS:  The delay in clinical worsening seen in patients taking tadalafil 40-mg over the 68-week treatment period is consistent with the improvement in 6MW distance seen over this time, and suggests durable clinical benefit for tadalafil in PAH treatment.

DISCLOSURE:  Ronald Oudiz, Consultant fee, speaker bureau, advisory committee, etc. - Lecture Fees/Honoraria from Actelion, Gilead, LungRx, Pfizer, United Therapeutics - Research Support for Actelion, Bayer, Gilead, Eli Lilly, LungRx, Pfizer, United Therapeutics -Mike Wade and Carl Arneson are employees of United Therapeutics Corp.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Tadalafil is not yet approved.

Tuesday, November 3, 2009

12:45 PM - 2:00 PM




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