Vasoactive Agents as Treatment-pulmonary hypertension

• PDE-5 inhibitor sildenafil, tadalafil, vardenafil ↑ cGMP → vasodilatation, ↓ smooth muscle proliferation, ↓ sx, ↑ 6MWT, no data on clinical outcomes. Often 1st line b/c minimal side-effect profile: HA, vision Δ’s, sinus congestion.
• Endothelin receptor antagonists (ERAs) bosentan, ambrisentan, macitentan ↓ Smooth muscle remodeling, vasodilatation, ↓ fibrosis, ↓ sx, ↑ 6MWT, ↓ worsening PAH or need for prostanoids w/ trend for ↓ PAH mortality (w/ macitentan). Side effects: ↑ LFTs, HA, anemia, edema, teratogen (NEJM 2013;369:809).
• IV prostacyclin epoprostenol (Flolan) Vasodilatation, ↓ plt agg, ↓ smooth muscle prolif; benefits ↑ w/ time (? vasc remodeling). ↑ 6MWT, ↑ QoL, ↓ mortality. Side effects: HA, flushing, jaw pain, abd cramps, N/V, diarrhea, catheter infxn.
• Prostacyclin analogs [iloprost (inh), treprostinil (IV, inh, SC)] Same mech as prostacyclin IV, but easier admin, ↓ side effects, w/o risk of catheter infxn. ↓ sx, ↑ 6MWT. Inh Rx w/ improved V/Q matching. Inh trepostinil ↑ 6MWT in ILD-PH (NEJM 2021;384:325).
• Prostacyclin receptor agonist (selexipag, PO) Indicated for WHO Group I to delay disease progression and risk of hospitalization. Add in WHO FC II & III (NEJM 2015;373:2522).
• Soluble guanylate cyclase stimulator riociguat NO-independent ↑ cGMP → vasodilatation, ↓ smooth muscle -proliferation, ↓ sx, ↑ 6MWT in PAH; ↓ sx, ↓ PVR, ↑ 6MWT in CTEPH (NEJM 2013;369:319 & 330)
• Oral CCB nifedipine, diltiazem Consider if ⊕ acute vasoreactive response. Not 1st line b/c side effects: HoTN, lower limb edema.