18th February 2025

Management of pulmonary hypertension

All patients with PH should be referred to a specialist centre with expertise in managing the condition. There are supportive and disease-specific treatments available in PH.

Supportive therapies are non specific and can be employed in the management of all cases of PH.

Disease-specific medical treatments are available for group I PH (PAH) and there are specific interventional treatments for group IV PH. The treatments used in PAH have been shown to have variable and sometimes negative effects on patients with groups II and III PH. As a result, the primary medical management of groups II and III PH focuses on optimisation of the underlying left heart (group II) or pulmonary disease (group III). Given the heterogeneous aetiology of group V PH, PAH-specific therapy is also not utilised in this.

Supportive therapies are similar to those utilised in any patient with a chronic respiratory condition:

• Smoking cessation advice and support
• Pulmonary rehabilitation
• Vaccinations (influenza, coronavirus, pneumococcal)
• Optimising nutrition
• Oxygen therapy if hypoxic
• Diuretics in treating fluid overload from right ventricular failure from PH
• Treating underlying comorbidities
• Psychosocial support

Management of group I PH (PAH)

Patients with suspected PAH will generally have undergone RHC in order to confirm the diagnosis. Vasoreactivity testing at the time of RHC is recommended in those with suspected idiopathic PAH, hereditary PAH and PAH associated with drugs and toxins. PAH associated with other conditions is often not vasoreactive and so testing is not indicated. 

Vasoreactivity testing involves administration of a short-acting vasodilator (e.g. inhaled nitric oxide or intravenous epoprostenol) and assessment of haemodynamic response. A test is positive (‘vasoreactive’) if there is a ≥10 mmHg reduction in mPAP to a value ≤40 mmHg, with increased/unchanged cardiac output and minimally reduced/unchanged systolic blood pressure.

Initial treatment is guided by whether vasoreactivity testing is positive or not:

• For those that are vasoreactive, a trial of calcium channel blockers is indicated
  • Options include amlodipine, nifedipine, felodipine and diltiazem
  • Response to treatment is assessed after three to six months with repeat RHC
• For those who are not vasoreactive or where there is an inadequate response to calcium channel blockers there are other targeted therapies available
  • Endothelin receptor antagonists (ERA): ambrisentan (oral), bosentan (oral), macitentan (oral)
  • Phosphodiesterase 5 inhibitors (PDE5I): sildenafil (oral), tadalafil (oral)
  • Soluble guanylate cyclase stimulators (SGCS): riociguat (oral)
  • Prostacyclin receptor agonists (PRA): selexipag (oral)
  • Prostacyclin analogues: beraprost (oral), treprostinil (oral, inhaled, subcutaneous or intravenous), iloprost (inhaled), epoprostenol (intravenous)

Treatment decisions are based on WHO functional class (WHO-FC) grade and patient risk (determined by numerous factors including 6MWT distance and NT-proBNP level). WHO-FC ranges from grade I (no limitation in physical activity) to grade IV, where patients are unable to carry out physical activity without symptoms.

Oral monotherapy, often with ERAs,  may be appropriate for patients with WHO-FC class I/early class II and low-risk PH.

WHO-FC class II and III disease with low or intermediate risk is usually treated with a combination of ERA and PDE5I, most commonly ambrisentan and tadalafil.

Rapid or progressive disease or WHO-FC class IV or high-risk PH should be treated with a regime containing a parenteral prostacyclin analogue; intravenous epoprostenol is the preferred agent. This is often in addition to the ERA and PDE5I combination.

Inadequate response to combination medical therapy should prompt referral for consideration and work up for lung transplantation.

Management of CTEPH (group IV PH)

All patients with CTEPH should be on lifelong therapeutic anticoagulation, most commonly warfarin.

First-line management is consideration of pulmonary endarterectomy if the patient is an operative candidate.

If the patient is not an operative candidate or has persistent/recurrent PH following endarterectomy, medical therapies used in PAH can be used. Riociguat and parenteral prostacyclin analogues are used based on WHO-FC class at the time of initiation of treatment. ERAs and PDE5Is are also regularly used in clinical practice, albeit off-label currently. An alternative to medical therapy is balloon pulmonary angioplasty in patients who are not operative candidates or have persistent/recurrent PH following endarterectomy.