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07-04-2014 | Cardiology | Article

Triple therapy shows promise for severe PAH


Free abstract

medwireNews: Results of a small pilot study among patients with severe pulmonary arterial hypertension (PAH) support the long-term benefits of upfront triple combination therapy, French researchers report.

The 19 patients (mean age 39 years, 89% women), who had PAH in New York Heart Association (NYHA) functional class (FC) III/IV with severe haemodynamic impairment, were treated with epoprostenol (intravenous up to a maximum of 16 ng/kg per minute), bosentan (125 mg twice daily) and sildenafil (20 mg three times daily) between December 2007 and July 2013.

After 4 months of treatment, Olivier Sitbon (Université Paris-Sud, Le Kremlin-Bicêtre) and co-researchers observed significant clinical and haemodynamic improvements in 18 of the 19 patients. Indeed, 17 patients had moved to FC I/II and their 6-minute walking distance (6MWD) had increased from an average of 227 metres to 463 metres. One patient had an emergency heart and lung transplant at month 3 and was not included in the follow-up analyses.

At the final follow-up visit, a mean of 32 months after treatment initiation, all 18 patients were in FC I/II and their average 6MWD had increased to 514 metres, which was a further significant improvement on the 4-month visit. Initial improvements in haemodynamic variables were also maintained to the final visit.

The researchers used the French equation to calculate expected survival rates of 75%, 60% and 49% at 1, 2 and 3 years, respectively. The actual values of 100% at all time points may be partly due to the significant increase in cardiac index (from 1.66 to 3.64 L/min per m2) and fall in pulmonary vascular resistance (from 1718 to 492 dyn/sec per cm5), they note.

Jaw pain, manageable headache, diarrhoea and flushing were the most commonly reported adverse events, which are typical of epoprostenol therapy. Two patients discontinued bosentan (at 11.5 and 31.5 months) due to asymptomatic liver enzyme elevation, but they were maintained in FC I/II using epoprostenol and sildenafil.

Writing in the European Respiratory Journal, Sitbon and co-authors say that the success of the triple regimen in these patients is “particularly relevant given that, despite increasing awareness, the majority of PAH patients are in NYHA FC III/IV at diagnosis, with a significant proportion being in NYHA FC IV.”

They conclude: “The findings of this pilot study provide preliminary evidence supporting the long-term benefits of upfront triple combination therapy in patients with severe PAH.”

medwireNews ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2014

By Laura Cowen, medwireNews Reporter

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