ABSTRACT

The evolving treatment of PAH To the uninitiated it may appear that there has always been a wealth of PAHspecific therapies available. However, it has only been in recent years that the therapeutic armoury to effectively manage PAH has dramatically increased; hence, historically poor survival rates. It was not until 1981 when heart-lung transplantation was introduced, that an effective treatment for PAH became available. Challenged by the limited number of organ donors, medical treatments have been sought, the most successful of which can now postpone the need for transplantation. Increasing interest in PAH has led to many advances in treatment. The 3rd World Symposium on Pulmonary Arterial Hypertension (Venice 2003) represented a significant event in the clinical management of PAH. At this time, an expert task force was able to review clinical trial data to determine the clinical efficacy of a broad range of therapeutic strategies. A published report arising from this meeting76 and subsequent expert guidelines published in Europe and North America,16-18 now provide clinicians with a strong evidence base to manage patients with PAH. Figure 5.1 synthesizes the latest expert advice published following the 2003 World Symposium76 and the most recent North American guidelines.18 In both cases, a grading system, based on the strength of clinical trial evidence for study design and efficacy, was applied to each treatment listed in this figure. Epoprostenol77,78 bosentan,79 inhaled iloprost,80 and sildenafil81 were all awarded the highest strengths of expert recommendation.18,76 Importantly, in a rapidly evolving therapeutic environment the choice of first-line therapy for patients with symptomatic PAH now involves a combination of prostacyclin

analogues, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. In this context, choice of therapy takes into consideration, evidence, clinical judgement, regulatory approval, mode of administration, adverse event profile, cost, and patient preferences. The role and purpose of these treatments are overviewed, tabulated, and presented in more detail in Table 5.1.