If calcium channel blockers fail to control PAH, which treatment options may be used?

• A. ACE inhibitors
• B. Beta-blockers
• C. Calcium channel blockers
• D. Bosentan, prostaglandins, or sildenafil

Answer: (D)

When calcium channel blockers do not control PAH, the next step is to use PAH-specific therapies that target the key disease pathways. Bosentan, an endothelin receptor antagonist, reduces endothelin-1–mediated vasoconstriction and vascular remodeling, helping to lower pulmonary pressures and improve symptoms. Prostacyclin pathway agents (prostacyclin analogs) provide potent pulmonary vasodilation and have anti-platelet and anti-proliferative effects; they can be given in multiple routes (intravenous, subcutaneous, inhaled, or oral, depending on the drug) and are especially beneficial in more advanced PAH. PDE-5 inhibitors like sildenafil boost the NO–cGMP signaling in the pulmonary vasculature, promoting vasodilation and improving functional capacity. These therapies are the standard targeted options after CCB failure and may be used alone or in combination. In contrast, ACE inhibitors or beta-blockers are not PAH-specific treatments, and continuing CCB therapy would not address the underlying pathophysiology when CCBs have failed.