treatment of pulmonary hypertension
Last edited 08/2022
- Diuretics are needed to control oedema from right heart failure and home oxygen to correct hypoxia.
- Anticoagulation is recommended in pulmonary arterial hypertension (PAH) and is essential for patients with chronic thromboembolic pulmnary hypertension (CTEPH).
- Primary (idiopathic) pulmonary hypertension is treated with anticoagulants (because it is virtually impossible to rule out persistent micro-emboli as the cause).
- Calcium channel blockers are indicated in a small subset of patients with idiopathic hypertension who show a vasoreactive response at right heart catheterisation.
- In patients with group 1 pulmonary arterial hypertension (idiopathic PAH, PAH associated with connective tissue disease - predominantly seen with scleroderma) (1).
- Specific drugs have been found to be beneficial in randomised controlled trials with improvement in symptoms, delayed disease progression and improved survival.
- There are three main drug classes: prostanoids delivered iv, by nebuliser or subcutaneous (eg epoprostenol, iloprost, treprostinil), endothelin receptor antagonists (eg bosentan, ambrisentan), and phosphodiesterase inhibitors (eg sildenafil, tadalafil).
- These drugs are only prescribed through the designated centres.
- Side effects include flushing, headaches, gastro-intestinal disturbance and hypotension.
- Endothelin receptor antagonists require monthly liver function monitoring.
- Treatment of choice for patients with CTEPH is pulmonary endarterectomy (PEA) surgery.
- Lifelong anticoagulation is also recommended; antiplatelet therapy is not an alternative.
- Majority of patients can be cured with normalisation of pulmonary pressure following surgery with improvement in symptoms and prognosis, with a > 90% 5 year survival.
- Patients unsuitable for pulmonary endarterectomy surgery and patients who still have residual PH following pulmonary endarterectomy surgery might be considered for treatment with the drugs described above.
Endothelin receptor antagonists
- A systematic review concluded (1)
- endothelin receptor antagonists probably increase exercise capacity, improve World Health Organization functional class (a measurement
of how severe a person's pulmonary hypertension symptoms are), and may improve death rates and symptoms in people with PAH;
however they may also increase the risk of liver damage, although this was rare.
In selected patients who have class 4 symptoms despite optimal medical therapy, bilateral lung or heart lung transplantation may be considered. The 5 year survival following transplantation is approximately 50-60%.
- A meta-analysis showed evidence an improvement of survival in the patients treated with the targeted therapies approved for pulmonary arterial hypertension (2).
- With respect to the effects of the different classes of drugs (prostanoids, thromboxane synthase inhibitors, endothelin receptor antagonists, and phosphodiesterase type-5 inhibitors), no statistically significant between-group heterogeneity emerged in subgroup analyses in total mortality or between the subgroups testing each of the treatments.
- The clinical classification of pulmonary hypertension is helpful in understanding the different aetiology and determining treatment (3):
- Group 1 Pulmonary arterial hypertension (PAH)
- idiopathic PAH
- PAH associated with connective tissue disease: predominantly seen with scleroderma
- Group 2 Left heart disease
- PH associated with left heart dysfunction, systolic, diastolic or valve disease
- Group 3 Lung disease
- PH in patients with COPD or interstitial lung disease
- Group 4 Chronic thromboembolic pulmonary hypertension
- Group 5 Unclear and multifactorial mechanisms
- Rare diseases.
- World Health Organization classification functional status in primary pulmonary hypertension:
- class I - no limitation on physical activity functional
- class II - slight limitation functional class
- III - pronounced limitation functional
- class IV - inability to carry out any physical activity without symptoms.
- (1) Liu C, Chen J, Gao Y, Deng B, Liu K. Endothelin receptor antagonists for pulmonary arterial hypertension. Cochrane Database Syst Rev. 2021 Mar 26;3(3):CD004434. doi: 10.1002/14651858.CD004434.pub6. (Accessed on 15 Aug 2022).
- (2) Galie N et al. A meta-analysis of randomized controlled trials in pulmonary arterial hypertension Eur Heart J. 2009 Feb;30(4):394-403.
- (3) British Heart Foundation (June 2022). Lungs under pressure: Impact of BHF support for pulmonary hypertension research. Available at https://www.bhf.org.uk/what-we-do/our-research/impact-of-pulmonary-hypertension (Accessed 15 Aug 2022).