Pulmonary Hypertension Drugs
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Direct answer
Vasoreactivity testing at right heart catheterisation decides the first fork in pulmonary arterial hypertension: only the roughly one in ten idiopathic patients whose pressures fall with inhaled nitric oxide or intravenous adenosine may safely take calcium channel blockers — everyone else needs pathway-specific therapy. Three vasoactive systems are drugged: endothelin (bosentan, macitentan, ambrisentan), nitric oxide-cGMP (sildenafil, tadalafil, and the soluble guanylate cyclase stimulator riociguat, never combined with PDE5 inhibitors) and prostacyclin (epoprostenol, treprostinil, selexipag). Upfront combination therapy is standard for most. Crucially, these agents serve group 1 disease; left-heart and lung-disease hypertension need the cause treated, not pulmonary vasodilators.
What you must remember
- Five-group clinical classification: group 1 PAH (idiopathic, connective tissue disease, congenital shunts), group 2 left heart, group 3 lung disease, group 4 chronic thromboembolic (CTEPH), group 5 miscellaneous — therapy follows the group.
- Vasoreactivity criteria: mean pulmonary pressure fall of at least 10 mmHg to 40 mmHg or below with preserved cardiac output; only 10-15 per cent of idiopathic PAH qualify, and fewer sustain CCB benefit.
- Endothelin antagonists: bosentan needs monthly liver function tests and is teratogenic; ambrisentan causes oedema; macitentan 10 mg daily carries outcome evidence.
- NO pathway drugs: sildenafil 20 mg three times daily, tadalafil 40 mg daily; riociguat stimulates soluble guanylate cyclase — combining it with a PDE5 inhibitor causes hypotension and is prohibited.
- Prostacyclins: intravenous epoprostenol (continuous pump, highest-risk patients), treprostinil by subcutaneous, inhaled or oral routes, selexipag as an oral IP-receptor agonist.
- Combination evidence: ambrisentan plus tadalafil upfront (AMBITION) beats sequential monotherapy for event-free survival.
- CTEPH: operable disease goes to pulmonary endarterectomy; riociguat serves inoperable or residual disease — and anticoagulation continues.
Choosing initial therapy by risk
Risk drives intensity. A low-risk patient — walking well, right atrial pressure normal, cardiac index preserved — starts on oral combination therapy, typically an endothelin antagonist with a phosphodiesterase-5 inhibitor, with reassessment at three to six months. A high-risk patient in WHO class III-IV with a falling cardiac index goes straight to triple therapy including parenteral epoprostenol, because the prostacyclin pathway carries the strongest evidence in advanced disease. The calcium channel blocker belongs only to the proven vasoreactive minority; given blindly, it worsens outcomes by dropping systemic pressure and cardiac output while barely touching the pulmonary bed.
The negative lesson matters equally in the ward. The breathless patient with mitral stenosis (group 2) or advanced COPD (group 3) has pulmonary hypertension, but pulmonary vasodilators have nothing to offer and hypotension to add; correcting the valve or the lung is the therapy.
Indian access and rationale
Indian generic sildenafil transformed group 1 care: 20 mg three times daily became affordable where imported prostacyclins never will be, and sildenafil is NLEM-listed for pulmonary arterial hypertension. Bosentan, macitentan and epoprostenol stay confined to referral centres — AIIMS, PGIMER and private transplant programmes — making early referral part of the prescription. CTEPH from untreated deep vein thrombosis or antiphospholipid syndrome remains a distinctly Indian presentation; diligent anticoagulation in the first VTE prevents the pulmonary vascular disease a decade later. Report riociguat hypotension and ambrisentan oedema to the PvPI.
Frequently asked questions
Who may receive calcium channel blockers in pulmonary arterial hypertension?
Only patients with a positive acute vasoreactivity test at catheterisation — about 10-15 per cent of idiopathic PAH — re-assessed for sustained benefit at follow-up.
Which two drug classes must never be combined?
Riociguat and PDE5 inhibitors — dual stimulation of the NO-cGMP pathway produces profound hypotension; the combination is explicitly prohibited.
What monitoring does bosentan require?
Monthly liver function tests and monthly pregnancy testing in women of childbearing age; hepatotoxicity and teratogenicity are its twin constraints.
Which drug serves inoperable chronic thromboembolic pulmonary hypertension?
Riociguat — after surgical candidacy is excluded by a specialised endarterectomy team; anticoagulation continues throughout.
Why are PAH drugs withheld in groups 2 and 3?
Their disease follows left-heart pressures or hypoxic lung disease; pulmonary vasodilators add hypotension and shunt without outcome benefit.