Observational trials in pulmonary arterial hypertension: low scientific evidence but high clinical value.

I n this issue of the European Respiratory Journal, MATHAI et al. [1] (from Johns Hopkins University, Baltimore, MD, USA) report on their experience with the use of sildenafil, a phosphodiesterase-5 inhibitor, in patients with pulmonary arterial hypertension (PAH) who failed monotherapy with bosentan, an endothelin receptor antagonist. Within a 4-yr period, 82 patients with either idiopathic PAH (IPAH) or PAH associated with systemic sclerosis (PAH-SSc) were treated with bosentan. Among those, 13 IPAH patients and 12 PAH-SSc patients showed signs of clinical worsening such that sildenafil was added to bosentan. Although haemodynamic parameters were similar at baseline, the median time from initiation of bosentan treatment to clinical worsening was 792 days in the IPAH group but only 458 days in the PAH-SSc group. The clinical response to combination therapy was mixed: in IPAH patients, the 6-min walk distance improved by 47¡77 m, whereas in PAH-SSc patients the 6-min walk distance deteriorated by -7¡40 m. During follow-up, only one IPAH patient needed additional therapy (intravenous treprostinil), whereas five PAH-SSc patients required further escalation of treatment by addition of either inhaled or intravenous prostanoids. Death occurred in one IPAH patient (from gastro-intestinal bleeding unrelated to PAH) and in four patients with PAH-SSc. MATHAI et al. [1] thus concluded that addition of sildenafil to bosentan was more effective in patients with IPAH than in patients with PAH-SSc and that additional studies are needed to assess safety and efficacy of this combination in the latter group of patients.