Pulmonary vasodilator therapy
Pulmonary vasodilator therapy is the endothelin receptor antagonists, phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, and prostacyclin-pathway drugs used to treat World Health Organization group 1 pulmonary arterial hypertension once right heart catheterization confirms the diagnosis. Oral combination therapy, most often an endothelin receptor antagonist paired with a phosphodiesterase-5 inhibitor, is first-line for most patients, while parenteral epoprostenol is reserved for severe or rapidly progressive disease.
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What this article covers
- Overview
What the class treats: endothelin receptor antagonists, phosphodiesterase-5 (PDE5) inhibitors, soluble guanylate cyclase (sGC) stimulators, and prostacyclin-pathway agents treat World Health…
- Epidemiology
How widely used: prescribed only after catheterization confirms group 1 PAH, a minority of all pulmonary hypertension; left-sided heart disease causes 65% to 80% of pulmonary hypertension, managed by…
- Risk factors
Connective tissue disease: systemic sclerosis, especially limited cutaneous disease, carries the highest risk; rheumatoid arthritis and lupus are rarer.
- Pathophysiology
In PAH, imbalance among nitric oxide, prostacyclin, and endothelin signaling in the small pulmonary arterioles drives vascular narrowing, smooth muscle proliferation, and endothelial dysfunction…
- Clinical features
PDE5 inhibitors (sildenafil, tadalafil): headache, flushing, dyspepsia, visual or hearing disturbance; contraindicated with a nitrate or riociguat.
- Differential diagnosis
High-dose calcium channel blocker versus a PAH-specific agent: reserved for the minority with a marked pressure fall to inhaled nitric oxide, epoprostenol, or adenosine at catheterization; unlike a nonresponder, who gains nothing from it.
- Diagnosis
What confirms the candidate for therapy: the diagnosis is made by right heart catheterization showing a resting mean pulmonary artery pressure of 20 mmHg or greater, elevated pulmonary vascular…
- Management
First-line, for functional class II to III disease, start oral combination therapy from two pathways: Ambrisentan 5 mg PO once daily, increasing to 10 mg once daily if tolerated, plus tadalafil 40 mg PO once daily is the preferred pairing.
- Complications
Right ventricular failure: compensated RV remodeling decompensates as disease advances, producing jugular venous distention, hepatomegaly, ascites, and peripheral edema; persistent atrial fibrillation in PAH raises mortality risk.
- Prognosis
Vasoreactive patients: survival with calcium channel blockers exceeds that of other patients with PAH, although many lose vasoreactivity within a few years.
- Prevention
Confirm before treating: never start a vasodilator or high-dose calcium channel blocker before catheterization confirms a mean pulmonary artery pressure of 20 mmHg or greater with elevated PVR.
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