What are the management options for pulmonary hypertension?

Management of Pulmonary Hypertension

The management of pulmonary hypertension requires a specialized approach at centers with expertise in PH diagnosis and treatment, with medication therapy tailored to the specific PH classification, risk category, and vasoreactivity status of the patient. 1

Classification and Initial Assessment

Pulmonary hypertension is defined as a mean pulmonary artery pressure >20 mmHg and is classified into five main groups:

1. Pulmonary arterial hypertension (PAH, WHO Group 1)
2. PH due to left heart disease
3. PH due to lung disease
4. PH due to pulmonary artery obstructions (often thromboembolic)
5. PH with unclear/multifactorial mechanisms

Risk assessment is essential for treatment decisions, based on:

• WHO functional class (I-IV)
• 6-minute walk distance
• Right ventricular function
• BNP/NT-proBNP levels

Pharmacological Management

Vasoreactivity Testing and CCBs

• Calcium channel blockers (nifedipine, diltiazem, amlodipine) are recommended for vasoreactive patients, though only ~10% of IPAH patients respond to CCBs 1

First-Line Therapy

• For treatment-naïve PAH patients with WHO FC II and III symptoms, initial combination therapy with an endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5I) is recommended 1
• Common combinations include:
  • Ambrisentan + tadalafil
  • Bosentan + sildenafil

Medication Classes

1. Endothelin Receptor Antagonists (ERAs):

   • Bosentan, ambrisentan, macitentan
   • Require liver function monitoring
   • Note: Bosentan has drug interactions with sildenafil and hormonal contraceptives 1

2. Phosphodiesterase-5 Inhibitors (PDE5Is):

   • Sildenafil (20 mg three times daily)
   • Tadalafil (40 mg once daily)
   • Contraindicated with nitrates 1

3. Soluble Guanylate Cyclase Stimulator:

   • Riociguat 1

4. Prostacyclin Pathway Agents:

   • Epoprostenol (IV): First-line for high-risk/WHO FC IV patients 1, 2
   • Treprostinil (IV, subcutaneous, inhaled, oral)
   • Iloprost (inhaled)
   • Selexipag (oral prostacyclin receptor agonist) 1

Sequential Combination Therapy

• For patients with inadequate response to dual therapy, addition of a third drug class is recommended 3, 1
• Options include adding inhaled treprostinil, inhaled iloprost, or riociguat to improve 6MWD, WHO FC, and delay clinical worsening 1

High-Risk Patients (WHO FC IV)

• Intravenous epoprostenol is the treatment of choice 1, 2
• Epoprostenol improves exercise capacity, hemodynamics, and survival in severe PAH 2
• Dosing: Start at 2 ng/kg/min, increase by 2 ng/kg/min every 15 minutes until dose-limiting effects occur 2
• Maintenance: Increase by 1-2 ng/kg/min at intervals of at least 15 minutes based on clinical response 2
• Requires continuous IV administration via central venous catheter using an ambulatory infusion pump 2

Non-Pharmacological Management

General Measures

• Avoid pregnancy (contraindicated due to 30-50% mortality risk) 3, 1
• Avoid high altitude exposure 3
• Use supplemental oxygen during air travel to maintain saturations >91% 3
• Immunization against influenza and pneumococcal infection 1
• Avoid non-essential surgery 3

Surgical Considerations

• When surgery is necessary, care should be at a pulmonary hypertension center 3
• Multidisciplinary approach including pulmonary hypertension team, surgical service, and cardiovascular anesthesiology 3
• Careful monitoring of clinical status, oxygenation, and hemodynamics postoperatively 3

Advanced Therapies

• Lung transplantation for patients with inadequate response to maximal medical therapy 1
• Atrial septostomy may be considered for refractory patients 1

Monitoring and Follow-up

• Regular assessment of treatment response using:

  • WHO functional class
  • 6-minute walk distance
  • Right ventricular function assessment
  • BNP/NT-proBNP levels 1

• Risk stratification for prognosis:

  Risk Category	1-Year Mortality	Key Characteristics
  Low Risk	<5%	WHO FC I-II, 6MWD >440m, No RV dysfunction
  Intermediate	5-10%	WHO FC III, 6MWD 165-440m, Moderate RV dysfunction
  High Risk	>10%	WHO FC IV, 6MWD <165m, Severe RV dysfunction

Special Considerations

• Liver function monitoring is essential for patients on ERAs, particularly bosentan 1
• Drug interactions: PDE5Is with nitrates (contraindicated), bosentan with sildenafil (decreased sildenafil levels), bosentan with cyclosporine (contraindicated) 1
• Anticoagulation may be required, with warfarin dose potentially needing adjustment when used with certain PAH medications 1

Referral to Specialized Centers

Management at specialized PH centers is crucial, with requirements including:

• Dedicated PH physicians
• Clinical nurse specialists with PH expertise
• Radiologists with expertise in PH imaging
• Expertise in echocardiography and right heart catheterization
• Access to psychological and social work support 1