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Pulmonary arterial hypertension (PAH) is a complex disease leading to right ventricular (RV) failure and death, because of a proliferative vascular remodeling that obstructs the lumen of resistance pulmonary arteries (PA). Despite tremendous investments from the scientific community and industry over the past 20 years, the disease remains deadly.1 Currently approved therapies act mainly as vasodilators that cannot reverse the disease or improve survival, while they are offered at a prohibitive cost for many patients.1 Is the field in crisis? Kuhn2 described scientific crisis as a state where there is loss of confidence in the current paradigm while alternative, more attractive theories emerge and social pressures push toward a new outlook and proposed that these conditions promote a paradigm shift. The PAH community is losing confidence in the current paradigm, ie, the use of vasodilators as therapy for PAH, a disease in which vasoconstriction plays only a minor role. Yet, more drugs from the same families (endothelin receptor antagonists, activators of the NO/cGMP axis, or prostacyclin analogues) continue to be developed, tested, and approved. Although these drugs may also affect apoptotic and proliferation mechanisms, their primary mode of action is vasodilation. The proproliferative and antiapoptotic environment within the PA wall can be explained by a myriad of molecular abnormalities discovered in preclinical research, many of which show translational promise as targets for novel therapies.1 But none has been approved, and only a small fraction enters clinical trials.1Translation to early-phase trials is a challenging stage in drug development, and many bottlenecks have been identified.1 Instead of intensifying efforts to develop novel drugs that target the foundation of PAH’s pathology, the development of vasodilators remains attractive for industry. Although vasoconstriction is not an important factor for most PAH patients, it contributes to a small degree …

A Paradigm Shift Is Needed in the Field of Pulmonary Arterial Hypertension for Its Entrance Into the Precision Medicine Era