Recent advances in the management of pulmonary arterial hypertension: lessons from the upfront combination of ambrisentan and tadalafil

INTRODUCTION: The sixth World Symposium of Pulmonary Hypertension (sixth WSPH) brought to the forefront for the first time the value of earlier, aggressive management with an upfront oral combination in patients with pulmonary arterial hypertension (PAH) of low or intermediate risk. This was prompted by results from the AMBITION study (ambrisentan + tadalafil). A literature search was conducted to collect all evidence provided by upfront treatment with this combination, as well as other combinations under investigation at the time the manuscript was prepared. AREAS COVERED: The value of an upfront oral combination with ambrisentan and tadalafil is reviewed on the basis of topics discussed at the sixth WSPH, such as evidence in different PAH etiologies, according to risk stratification and in so-called 'atypical' patients where monotherapy is still recommended. Evidence in clinical practice is also reviewed. New evidence about the value of the upfront oral combination is also commented. Finally, tendencies in primary endpoints to assess the effect of PAH-targeted therapies (time to clinical worsening and hemodynamics) and their value are also reviewed. EXPERT OPINION: All above-mentioned aspects are put into perspective with regard to the impact of new advances on improving PAH management in clinical practice.