Upfront combination therapy fulfils AMBITION in PAH patients

By Eleanor McDermid, Senior medwireNews Reporter

Upfront treatment with the combination of ambrisentan and tadalafil improves outcomes in patients with pulmonary arterial hypertension (PAH) more than either treatment as monotherapy, shows a randomised trial.

Rather than giving combination therapy as adjunctive treatment if response to monotherapy was not satisfactory, the investigators of the AMBITION trial gave it to patients newly diagnosed with PAH, who had previously received treatment for less than 14 days or not at all.

This strategy led to around a 50% reduction in the primary endpoint of first clinical failure event, with such events comprising death, hospitalisation for worsening PAH, disease progression or a poor long-term clinical response.

The 253 patients assigned to receive combination therapy had a primary endpoint rate of 18%, compared with 34% for the 126 given ambrisentan plus placebo and 28% for the 121 given tadalafil plus placebo.

Nazzareno Galiè (University of Bologna, Italy) and co-researchers found that the positive effect of combination therapy was driven mainly by a reduced rate of hospitalisation for PAH, at 4% among patients given combination therapy versus 14% and 10% among those given ambrisentan monotherapy and tadalafil monotherapy, respectively.

“Hospitalization for worsening pulmonary arterial hypertension is costly and is associated with a poor prognosis”, the team observes in The New England Journal of Medicine.

The first difference in outcome rates between combination treatment and monotherapy was seen at week 24 – the point at which long-term clinical response was assessed. At this point, 39% of the combination therapy group had a satisfactory response, compared with 31% in the ambrisentan group and 27% in the tadalafil group.

Study participants continued to use a randomly assigned study medication for about 73 weeks on average. After 144 weeks of follow-up, the difference in the primary outcome rates between the groups appeared to decline, which the researchers say could suggest “a waning beneficial effect of initial combination therapy” over time, but could also be because the number of patients left in the study by this point was “insufficient to allow a meaningful comparison.”

They conclude: “The AMBITION trial supports the rationale for targeting multiple pathways in pulmonary arterial hypertension and showed that early combination therapy can be beneficial.”

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