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07-11-2016 | Pulmonary hypertension | News | Article

AMBITION analysis hints at PAH survival benefit with upfront combination therapy

medwireNews: A post-hoc analysis of the AMBITION trial raises the possibility that upfront combination therapy could have a beneficial effect on the survival of patients with pulmonary arterial hypertension (PAH).

“Given the fundamental implications, this question should be addressed in future studies,” say the researchers.

The prespecified analysis included all 605 patients in the trial, who were treatment-naïve at enrollment, including those who withdrew from treatment early and were followed up only for survival. Among these patients, 10% of patients who received combination therapy with ambrisentan and tadalafil died over a median 101 weeks of follow-up, compared with 14% of those given ambrisentan or tadalafil only and followed up for a median of 96 weeks.

The hazard ratio for mortality was 0.67, but the 95% confidence interval was 0.42 to 1.08 and therefore not statistically significant (p=0.10).

But in a post-hoc analysis, Marius Hoeper (Hannover Medical School and German Centre for Lung Research) and co-researchers assessed the survival of patients up until 7 days after they stopped treatment, whenever in the trial that was. This was based on an analysis conducted in the SERAPHIN trial, which the team says was presumably designed “to capture events that were more likely to be related to the originally assigned treatment.”

In this analysis, the mortality rates were much lower, at 1% versus 4% in the combination and monotherapy groups, respectively. This gave a significantly reduced hazard ratio for mortality of 0.21 (p=0.0065), the researchers report in The Lancet Respiratory Medicine.

In a commentary accompanying the study, Paul Hassoun (Johns Hopkins University School of Medicine, Baltimore, Maryland, USA) describes the findings as “thought provoking,” saying that they “strongly raise the possibility that a radically different therapeutic approach (ie, upfront combination therapy) might improve the only meaningful endpoint (ie, death) in this disease.”

He notes the several weaknesses of the study, stemming from the post-hoc nature of the analysis, but hopes that the work “will inspire investigators, industries, and regulatory agencies alike to finally consider death as the most relevant endpoint in this disease, despite the obvious challenge of conducting trials of even longer duration to achieve this important goal.”

By Eleanor McDermid

medwireNews is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2016