Guest Editor's Memo
A quick review of the history of medical therapy for PAH reveals a dramatic evolution from essentially 0 therapies to now 15 therapies - accounting for various routes of administration, preparations, and manufacturers. This evolution occurred over slightly more than 2 decades. The use of these medications and treatment guidelines has also followed a parallel evolution with several iterations in the same time frame. Accruing knowledge and evidence shapes guidelines but optimal treatment of patients with a rare disease that has significant clinical heterogeneity remains a challenge. Additional factors impeding all-inclusive guidelines are: absence of a cure; widely varying risk-benefit considerations of different therapies and delivery methods; and a wide spectrum of patient-centric goals given these factors.
Clinical trials in PAH have not and may never fully address the spectrum of presentations, combinations, options, and goals of therapy. Understanding this, treatment of patients is approached with combinations of experience and evidence which is the focus of this and the next issue of Advances.
We attempt to survey topics starting with an exposition of guideline writing in PAH by Dr. James Klinger in the “Ask the Expert” section Part I of this 2-part issue. After this introduction, we have attempted to survey across the spectrum of therapeutic approaches and guideline recommendations, focusing on areas where evidence is incomplete and decisions may require significant elements of experience. These topics range from evaluation of vasoreactivity and calcium channel blocker therapy, evaluation of monotherapy options to more recent dilemmas outlined by Dr. Frantz - the positioning of new therapeutic agents such as riociguat, selexipag and oral treprostinil in the current landscape of treatment option. We have attempted to tie these presentations to sections of the European Society of Cardiology and European Respiratory Society's guidelines to provide context for the specific focus areas of this issue and as a way of thinking about integrating guidelines into practice.
Our roundtable discussion, which appears in the forthcoming Part 2 of this double issue, assembles physicians with an aggregate of more than 100 years of experience in treating patients with PAH spanning 2+ decades. We are joined by Drs. Robert Bourge, Richard Channick, and Srinivas Murali in a lively discussion of topics ranging from treatment strategies, assessment of risk, goal setting, escalation of therapy to the balance of experience and evidence and guidelines in our current era of therapeutic choices for the management of PAH.
The next issue in this series will include topics such as combination and infusion prostacyclin therapies. In addition, we are pleased that Dr. Harrison Farber (Hap), the next Editor-in-Chief of Advances, has agreed to provide a “wrap-up” assessing the current state of guidelines and their contribution to daily treatment decisions, provocatively titled: “PAH guidelines: What we know, what we don't, and what we wish we did.” We hope that these issues provide a unique and thought-provoking perspective on familiar topics and address some of the gaps and limitations of guideline documents.