A Concerning Trend for Patients With Pulmonary Hypertension in the Era of Evidence-Based Medicine

ulmonary hypertension (PH) is an abnormal elevation in pulmonary arterial blood pressure. Regardless of the underlying cause, PH is an independent risk factor for adverse outcome. Pulmonary arterial hypertension (PAH) is a rare form of PH, which is characterized by plexogenic vascular remodeling. Although therapeutic advances have been made in PAH, currently there are no approved therapies for PH from left-sided heart disease (World Health Organization [WHO] group 2) or chronic hypoxic lung disease (WHO group 3) PH. The importance of this treatment gap is amplified when considering that the prevalence of WHO group 2 or 3 is >2500-fold greater than PAH. Furthermore, the elevated pulmonary artery pressure in patients with WHO group 2 and 3 PH corresponds to an adjusted mortality risk increase of 50%. Specifically, the efficacy of endothelin receptor antagonists and phosphodiesterase type V inhibitors has been assessed in numerous observational studies and some prospective clinical trials involving patients with WHO group 2 or 3 PH (Table ). Although data from some small studies may appear encouraging, overall, these data have prompted a class III recommendation (treatment is not useful or effective, and may be harmful) from international expert consensus panels for the use of PAH therapy in patients with WHO group 2 or 3 PH. In the Giessen PH registry, published in 2017, from one of the world's leading PH centers, 40% of patients referred to the center with a diagnosis of WHO group 2 PH were on PAH therapies. In patients referred for WHO group 3 PH, 78% were on PAH therapies. In addition, a recently published population-based cohort study in Ontario, Canada showed that phosphodiesterase type V inhibitor was cumulatively prescribed for more patients with WHO group 2 PH than patients with PAH, and the use of phosphodiesterase type V inhibitors and endothelin receptor antagonists continues to rise in this cohort. It is particularly sobering that, in both of these studies, the prognosis was poorer in patients with WHO group 2 and WHO group 3 PH than in patients with PAH. Although speculative, it is worth considering whether this is attributable, at least in part, to the frequent use of contraindicated PAH medicines. These medicines affect systemic vascular beds as well, which may result in adverse hemodynamic consequences.