What combination therapy is recommended for patients with low- or intermediate-risk features of pulmonary arterial hypertension?

The recommended combination therapy of a phosphodiesterase type 5 inhibitor and an endothelin receptor antagonist for patients with low- or intermediate-risk features of pulmonary arterial hypertension (PAH) is supported by clinical evidence indicating that such a strategy can enhance treatment efficacy through complementary mechanisms of action.

Phosphodiesterase type 5 inhibitors improve pulmonary vasodilation by increasing cGMP levels, while endothelin receptor antagonists inhibit the effects of endothelin-1, a potent vasoconstrictor. This combination approach targets different pathways involved in the pathophysiology of PAH, offering an opportunity to improve hemodynamics, exercise capacity, and overall functional status compared to single-agent therapy.

Utilizing oral combination therapy is particularly beneficial for managing low- to intermediate-risk patients, as it helps to optimize therapeutic outcomes while potentially minimizing symptoms and preserving quality of life. This aligns with current clinical guidelines, which recommend a multimodal approach in the management of PAH to achieve better control of the disease and improve patient prognosis.

In contrast, other options such as high-dose monotherapy or single therapy with a phosphodiesterase type 5 inhibitor may not provide the same level of benefit, as they may not address the