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First-line combination of Ambrisentan and Tadalafil reduces risk of clinical failure compared to monotherapy in pulmonary arterial hypertension

Data of the first phase IIIb/IV study, AMBITION, were presented at the ERS International Congress 2014. The study has investigated combination therapy of Ambrisentan and Tadalafil in treatment naïve patients with pulmonary arterial hypertension ( PAH ).

The randomised, double-blind, multicentre study has shown that first-line treatment of PAH with the combination of Ambrisentan 10 mg and Tadalafil 40 mg has reduced the risk of clinical failure by 50% compared to pooled Ambrisentan and Tadalafil monotherapy arm ( hazard ratio, HR= 0.502; p=0.0002 ).
The combination was also statistically significant versus the individual Ambrisentan and Tadalafil monotherapy groups for the primary endpoint.

Statistically significant improvements were also observed for three of the secondary endpoints ( 6 minute walk distance test, percentage of patients with satisfactory clinical response, change from baseline in N-terminal pro-B-type natriuretic peptide ).
The remaining two secondary endpoints ( WHO functional class and Borg dyspnea index ) did not meet statistical significance.
Rates of serious adverse events and events leading to discontinuation were similar across treatment arms.

Ambrisentan, a selective endothelin type-A receptor antagonist, and Tadalafil, a PDE-5 inhibitor, are each approved in the European Union ( EU ) and other countries as once-daily treatments for PAH, ( WHO Group 1 ) in patients with WHO/NYHA functional class II and III symptoms.
In the EU, Ambrisentan is indicated for the treatment of adult patients with PAH classified as WHO functional class II and III, to improve exercise capacity. Tadalafil is indicated in adults for the treatment of PAH classified as WHO functional class II and III, to improve exercise capacity.

PAH is a debilitating disease characterised by constriction of the blood vessels in the lungs leading to high pulmonary arterial pressures. These high pressures make it difficult for the heart to pump blood through the lungs to be oxygenated.
Patients with PAH suffer from shortness of breath as the heart struggles to pump against these high pressures, causing such patients to ultimately die of heart failure.
PAH can occur with no known underlying cause, or it can occur secondary to diseases such as connective tissue disease, congenital heart defects, cirrhosis of the liver and HIV infection.
PAH afflicts approximately 200,000 patients worldwide. ( Xagena )

Source: GSK, 2014