According to the AMBITION trial results, which initial therapy for pulmonary arterial hypertension would best be considered?

The AMBITION trial specifically explored the efficacy of up-front combination therapy in patients with pulmonary arterial hypertension (PAH). In this study, the combination of tadalafil, a phosphodiesterase-5 inhibitor, and ambrisentan, an endothelin receptor antagonist, demonstrated superior results compared to monotherapy in terms of reducing clinical worsening of the disease. This finding supports the use of dual therapy as an effective initial treatment approach for PAH, providing greater improvement in exercise capacity and patient outcomes.

Combining these two agents allows for a synergistic effect, addressing different pathophysiological mechanisms of PAH. Since they work through complementary pathways—tadalafil increasing nitric oxide availability and ambrisentan blocking endothelin-1 receptor effects—this combination can lead to improved vasodilation and reduced pulmonary vascular resistance.

The other treatment approaches do not reflect the findings of the AMBITION trial as effectively. Stepwise therapy, whether it entails adding ambrisentan to tadalafil or using epoprostenol followed by sildenafil, could delay optimal treatment, risking clinical worsening during the adjustment period. Furthermore, while triple therapy has its place in more advanced cases, it was not the focus of the AMBITION trial, which highlights the advantage of initiating treatment with