Targeted Therapies May Ease Severe Pulmonary Hypertension

Jim Kling

September 29, 2015

AMSTERDAM — Targeted therapies might decrease mortality in patients with group 3 pulmonary hypertension, according to a retrospective analysis.

The work, presented here at the European Respiratory Society International Congress 2015, was inspired after Tobias Lange, MD, from Regensburg University Hospital in Germany, noticed that some of his patients treated with these drugs seemed to be living longer.

His team assessed endothelin-receptor antagonists and prostacyclin analogues, which are approved for the treatment of pulmonary arterial hypertension, and phosphodiesterase 5 inhibitors, which are approved for the treatment of erectile dysfunction.

None of these drugs are approved for group 3 pulmonary hypertension. Previous studies that have assessed their short-term benefits, such as improved lung function, in patients with group 3 pulmonary hypertension have shown no effect.

In fact, to date, none of these treatments have been shown to have clinical benefit in this group of patients, so the decision to use them must be on a case-by-case basis, Dr Lange explained.

And short-term studies might not reveal potential benefits in this population, Dr Lange pointed out.

Controversial Options

The team assessed the 72 patients diagnosed with group 3 pulmonary hypertension, defined as mean pulmonary artery pressure of at least 25 mm Hg at rest, from January 2005 to September 2011. Exercise capacity, survival, and targeted therapy use in the study cohort were followed until April 2012.

Half the patients in this analysis had chronic obstructive pulmonary disease, and the rest had a mixture of other lung conditions, including idiopathic pulmonary fibrosis, combined fibrosis and emphysema, chronic hypersensitivity pneumonitis, idiopathic nonspecific interstitial pneumonia, silicosis, and abnormalities of the thorax or diaphragm.

The 40 patients with severe pulmonary hypertension, defined as a mean pulmonary artery pressure of at least 35 mm Hg, were much more likely to receive targeted therapy than those with less severe pulmonary hypertension (65% vs 25%; P = .001).

There was a pronounced reduction in mortality in those with severe disease who were treated with targeted therapy. The positive mortality results are "just hypothesis-generating, but they're worth thinking about," Dr Lange said during a poster session here at the meeting.

Table: Association Between Survival and Targeted Therapy in Severe Pulmonary Hypertension

Estimated Survival Targeted Therapy, % (n = 26) No Targeted Therapy, % (n = 14) P Value
1 year 97 83 .002
3 years 81 54 .002
5 years 75 19 .002


The targeted therapy had no significant effect on exercise capacity.

Some degree of skepticism was expressed during the session, and many people said they would wait for prospective clinical trials to back up the finding before endorsing this approach.

"We need the clinical trials to not focus on 6-minute walking distance after 12 weeks. We need outcome trials," said session moderator Ardeschir Ghofrani, MD, from the University of Giessen in Germany.

The findings are interesting, said Joan Albert Barberà, MD, from the Hospital Clinic of Barcelona, who has conducted extensive clinical studies of patients with group 3 pulmonary hypertension. But he too called for prospective trials.

However, he also pointed out that the infrastructure required to conduct prospective trials makes it unlikely that this will be studied further.

When asked if physicians should consider using the targeted therapies in these patients in the absence of prospective data, Dr Barberà let out a sigh. "We don't know," he said, "and the guidelines are clear, so there is no information at present that justifies that."

This study received some support from Pfizer. Dr Lange reports financial relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer, Encysive, GlaxoSmithKline, Lilly, and Pfizer. Dr Ghofrani reports financial relationships with Actelion, Bayer, Ergonex, Pfizer, Bellerophon, GlaxoSmithKline, and Novartis. Dr Barberà reports serving on advisory boards for Actelion, Bayer, GlaxoSmithKline, and Pfizer.

European Respiratory Society (ERS) International Congress 2015: Abstract PA2101. Presented September 28, 2015.


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