2009, Volume 16, Supplement 1: Moving forward in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a comparatively rare, chronic, progressive disease of unknown aetiology, which is characterised by increased pulmonary vascular resistance and which may ultimately lead to right heart failure and premature death.1 In a recent French registry the estimated prevalence was 15 cases per million, with approximately twice as many women as men being diagnosed.2 PAH is increasingly diagnosed in older people, who may have considerable co-morbidities compared to the younger PAH patients traditionally seen.2 ...

Reviewing this topic, Professor Lewis J Rubin, University of California, San Diego, US, looked at both the successes and failures of the past 20 years. He described how, as little as two decades ago, there was no treatment algorithm for PAH: “we had absolutely no understanding of the fundamental mechanisms responsible for the development of PAH” and approaches to treatment were based on a simplistic extrapolation from systemic hypertension and left-sided heart disease. ...

Current data show that PAH patients are now older than previously reported, and more patients are identified with associated co-morbidities, according to Professor Marius Hoeper, Hannover Medical School, Germany. One recent study in more than one thousand patients showed that over one half had two or more co-morbidities.1 About one third had systemic hypertension, 16% had hypothyroidism, 15% scleroderma, 14% were clinically depressed (possibly as a consequence of pulmonary hypertension) and a further 13% had diabetes.1 Some centres also report that the spectrum of PAH patients seems to be changing, he said. Whereas in the past idiopathic PAH was more common, in recent years PAH in association with connective tissue disorders and congenital heart disease has been more frequently observed in many centres.2 The severity of pulmonary vascular resistance at presentation also seems to be (slightly) declining, which suggests that the disease is being diagnosed earlier. However, the vast majority of patients are still in functional class III or IV at diagnosis.2 Professor Hoeper emphasised the improvements in available medical treatments, which have broadened from the limited options of intravenous epoprostenol and calcium channel blockers to include a wide range of prostanoids and the newer drug classes of endothelin receptor antagonists (three are currently available in some countries) and PDE-5 inhibitors. ...

Professor Nazzareno Galiè, University of Bologna, Italy, outlined the pathophysiological mechanisms of pulmonary arterial hypertension (PAH). These are initiated by the progressive obstructive changes of the pulmonary resistance vessels which lead to the increase in afterload of the right ventricle (RV). In turn, this responds with functional and structural adaptations, leading ultimately to heart failure and death.1 The hope is to have some treatment to help in reverse remodelling. Over the past 15 years or so there have been 22 randomised controlled studies, using a variety of PAH agents. He showed some ‘hypothesis-generating’ data from trials, using historical controls (prior to 1992) and then including patients treated with prostacyclin and more recently (after 2000) with oral agents. Although these patients are not identical or comparable at baseline, it appears that survival of patients who are referred to us today is much better than survival 15 or more years ago,2 said Professor Galiè....

Professor Jean-Luc Vachiéry, Université Libre de Bruxelles, Belgium, began by looking at progress in the management of PAH over the last 50 years. Current therapies are now based on experience with earlier treatments, including calcium channel blockers1 and surgery,2 and by more recent, evidence-based RCTs with newer drugs (figure 1).3-5 We are facing different needs in a rapidly evolving field, according to Professor Vachiéry. He outlined the many emerging issues in PAH (table 1), which is an incurable disease.6 Unequivocally, patients need a cure and better quality of life with enhanced survival, while clinicians need evidence to guide treatment strategies. This must be balanced by healthcare regulators, who will be under pressure to control the costs, and also by industry, which has a huge responsibility in this field, especially as PAH is considered to be an orphan disease.7...