A New Day for PAH

Abstract

When the editorial board first considered an issue devoted to recent clinical trial results, clinicians had 6 FDA approved drugs to treat pulmonary arterial hypertension (PAH). We now have 7, and it seems conceivable that we might have an 8th before the end of 2009. With collaborative, international efforts, the pace of progress has quickened in the last 5 years, and indeed, a “New Day is Dawning” on treatment options for our patients.In this issue, Bob Schilz and I wanted to provide an authoritative update on recent clinical trials and to highlight therapies that have “graduated” from bench science to bedside investigation. An author on the pivotal epoprostenol report, David Langleben has a long perspective and remains committed to bench research on mechanisms of vascular dysfunction in PAH. His article highlights Phases I and II trial data that have been reported only in abstract form at international meetings in the last 2 years. He also invites readers to consider an important question about whether our current therapies address fundamental disease mechanisms. I think readers will especially appreciate the figure illustrating how cicletanine, riociguat, and phospho-diesterase inhibitors are related in the nitric oxide-cyclic GMP signaling pathway.Murali Chakinala's information-packed article summarizes key data from recently published or presented combination trials including PACES (adding sildenafil), TRIUMPH (adding inhaled treprostinil), and PHIRST (adding tadalafil). A useful table in the paper shows trends in the baseline characteristics of patients over the last decade, and his thoughtful analysis on endpoints highlights the limitations of our current approach in drug development and invites us to “Raise the bar” for future investigations.Finally, I reviewed the progress toward a highly effective oral prostanoid; unfortunately, I had to conclude that we as investigators have endured a large amount of backsliding down a steep learning curve. We still have a mountain to master!Scott Halpern has a research interest in the ethics of clinical research. We invited him to moderate a round table discussion with 3 leaders in clinical drug development over the last 20 years: Mike McGoon, David Badesch, and Myung Park. The questions were provocative, and I think you'll really learn from the lively dialogue among these authorities with very different perspectives.Bob Schilz and I enjoyed planning this issue, and we hope that it will serve as a valuable reference point for readers who wish to update their knowledge about the drugs (and cells!) that will heavily influence therapeutic approaches now and in the next 5 years.