Pulmonary arterial hypertension: Rationale for using multiple vs. single drug therapy

Pulmonary arterial hypertension (PAH) is defined by a heterogenous pathobiology that corresponds to variable clinical presentation, treatment response, and prognosis across affected patients. The approach to pharmacotherapeutics in PAH has evolved since the introduction of the first prostacyclin replacement drug, which was trialed in patients with end-stage disease as a strategy by which to delay or prevent mortality. Subsequently, the aim of care in PAH has shifted toward minimizing symptoms, improving functional capacity, delaying disease progression, and prolonging life. Thus, treatments are now implemented earlier and according to the evidence base, which spans more than twenty years and includes patients at various stages of disease. Overall, the evidence supports multidrug therapy rather than monotherapy in the majority of PAH patients. Among incident patients, up-front combination therapy with ambrisentan and tadalafil or other comparable agents within these drug classes is recommended based on strong clinical trial data. In the near future, up-front triple therapy may be emerge as bona fide treatment approach in selected patients. Future goals that are already under consideration in PAH include stronger integration of pathobiological characteristics when considering the use of specific drugs, or the development of novel therapies, toward precision medicine-based clinical pharmacology.