Figure 1:

Stepwise approach to managing pulmonary arterial hypertension (PAH) at Canadian expert centres, starting from bottom of the pyramid (based on the evidence described in Box 1). ^*Recommended only for patients whose pulmonary arterial hypertension meets specific criteria (idiopathic, heritable or drug-induced) and is identified as responsive to vasodilators by acute vasoreactivity testing during right-heart catheterization. ^†Options are phosphodiesterase type 5 inhibitors (PDE-5i; sildenafil, tadalafil) and soluble guanylate cyclase stimulators (sGC-S; riociguat), which improve signalling through the nitric oxide pathway; endothelin receptor antagonists (ERAs; bosentan, ambrisentan, macitentan), which block the action of endothelin-1; and a prostacyclin receptor agonist (selexipag), which addresses endogenous prostacyclin deficiency. Dual oral targeted combination therapy consists of one medication from the ERA family and another medication from either the PDE-5i family or the sGC-S family. ^‡Options include the synthetic prostacyclin analogues epoprostenol (intravenous) and treprostinil (intravenous or subcutaneous). NYHA-FC = New York Heart Association functional class, PH = pulmonary hypertension.