Ambrisentan Should NOT Be Used for Pulmonary Hypertension Due to COPD
Ambrisentan and other PAH-specific therapies are explicitly not recommended for pulmonary hypertension associated with lung diseases like COPD, as they have not demonstrated benefit and may cause harm. 1
Why PAH Drugs Are Contraindicated in PH Due to COPD
Lack of Evidence and Potential Harm
There is no evidence from randomized controlled trials suggesting that PAH drugs (including ambrisentan) result in improved symptoms or outcomes in patients with lung disease. 1
Published experience with targeted PAH drug therapy in lung disease-associated PH is scarce and does not support their use. 1
The 2015 ESC/ERS Guidelines explicitly state: "The use of drugs approved for PAH is not recommended for patients with PH due to lung disease." 1
Fundamental Pathophysiologic Differences
PH due to COPD (Group 3 PH) has fundamentally different pathophysiology than pulmonary arterial hypertension (Group 1 PAH), where ambrisentan is indicated. 1
In COPD, PH develops primarily from chronic hypoxemia, lung parenchymal destruction, and hypoxic pulmonary vasoconstriction—mechanisms not targeted by endothelin receptor antagonists. 1
What IS Recommended for PH Due to COPD
Appropriate Management Strategy
Long-term oxygen therapy is the primary treatment that has been shown to partially reduce the progression of PH in COPD, though pulmonary artery pressure rarely returns to normal values. 1
Optimize treatment of the underlying COPD with bronchodilators, inhaled corticosteroids, and pulmonary rehabilitation as indicated. 1
Conventional vasodilators such as calcium channel blockers are not recommended because they may impair gas exchange by inhibiting hypoxic pulmonary vasoconstriction. 1
When to Consider PAH-Specific Therapy (Rare Exception)
PAH-specific therapy may be considered only in highly selected patients with severe PH (mean PAP >35-40 mmHg) that is disproportionate to the severity of lung disease, suggesting a "PAH phenotype" with high pulmonary vascular resistance and low cardiac output. 2
These patients should have mild lung parenchymal abnormalities with symptoms insufficiently explained by lung mechanical disturbances. 1
Such patients require evaluation at a specialized pulmonary hypertension center with right heart catheterization to confirm the diagnosis and hemodynamic profile. 1
Evidence Supporting Ambrisentan in True PAH (Not COPD-PH)
Where Ambrisentan IS Indicated
Ambrisentan is recommended for pulmonary arterial hypertension (Group 1 PAH) including idiopathic PAH, PAH associated with connective tissue disease, congenital heart disease, and HIV. 1
The ARIES-1 and ARIES-2 trials demonstrated that ambrisentan improves 6-minute walk distance by 31-59 meters compared to placebo in PAH patients. 3
Ambrisentan is approved for WHO functional class II and III PAH patients at doses of 5-10 mg once daily. 1, 4
Critical Pitfall to Avoid
Do not extrapolate PAH trial data to COPD patients with PH. The single case report of ambrisentan use in combined pulmonary fibrosis and emphysema 5 represents anecdotal evidence that cannot override guideline recommendations against using PAH therapies in lung disease-associated PH. This case report involved a patient with severe precapillary PH who may have had a PAH phenotype rather than typical COPD-associated PH. 5