What is the treatment for pulmonary hypertension?

Treatment of Pulmonary Hypertension

Initial treatment for pulmonary hypertension should be guided by risk stratification, with low/intermediate risk patients receiving initial combination therapy with an endothelin receptor antagonist (ERA) and a phosphodiesterase-5 inhibitor (PDE5i), while high-risk patients should receive initial combination therapy including intravenous prostacyclin analogues. 1

Classification and Risk Assessment

Pulmonary hypertension (PH) is classified into five groups:

Group	Description
Group 1	Pulmonary Arterial Hypertension (PAH)
Group 2	PH due to left heart disease
Group 3	PH due to lung diseases/hypoxia
Group 4	Chronic thromboembolic PH (CTEPH)
Group 5	PH with unclear mechanisms

Risk stratification is crucial for treatment decisions:

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

Treatment Algorithm Based on Risk

Low/Intermediate Risk Patients (WHO FC I-III)

1. Initial Oral Combination Therapy:

   • ERA (ambrisentan, bosentan, macitentan) + PDE5i (sildenafil, tadalafil)
   • Preferred combination: ambrisentan plus tadalafil (shown superior to monotherapy) 1

2. Dosing for Key Medications:

   • Sildenafil: 20 mg three times daily 2
   • Selexipag: Start at 200 mcg twice daily, titrate weekly in 200 mcg increments to maximum tolerated dose up to 1,600 mcg twice daily 3
   • Bosentan: Start at 62.5 mg twice daily for 4 weeks, then 125 mg twice daily 1

3. If Inadequate Response:

   • Escalate to triple therapy by adding a prostacyclin analogue 1
   • Consider adding inhaled iloprost or treprostinil 1

High Risk Patients (WHO FC IV)

1. Initial Therapy:

   • IV epoprostenol (reduces 3-month mortality) 1, 4
   • Starting dose: 2 ng/kg/min with titration to dose-limiting effects 1
   • Consider combination with oral agents 1

2. Consider Advanced Options:

   • Atrial septostomy as bridge to transplantation 1
   • Lung transplantation for inadequate response to maximal therapy 1

Group-Specific Treatments

Group 1 (PAH)

• Combination therapy as outlined above
• Consider soluble guanylate cyclase stimulator (riociguat) as an option 1
• Caution: Never combine riociguat with PDE5i due to severe hypotension risk 1

Group 4 (CTEPH)

• Pulmonary endarterectomy (PEA) is treatment of choice for eligible patients 1
• Medical therapy for inoperable cases

Medication Monitoring and Precautions

• ERA therapy: Monitor liver function regularly 1
• Prostacyclin therapy: Avoid abrupt withdrawal (risk of rebound PH) 1
• Sildenafil: Contraindicated with nitrates; monitor for vision/hearing changes 2
• Selexipag: Reduce to once daily when co-administered with moderate CYP2C8 inhibitors 3
• Hepatic impairment:
  • Mild: No dose adjustment needed for selexipag
  • Moderate: Selexipag 200 mcg once daily, titrate weekly
  • Severe: Avoid selexipag 3

Regular Assessment and Follow-up

• Assessments every 3-6 months including:
  • WHO Functional Class
  • 6-minute walk distance (6MWD)
  • BNP/NT-proBNP levels
  • Echocardiography
  • Hemodynamic parameters when indicated 1

Supportive Care

• Supplemental oxygen to maintain saturations >91% 1
• Avoid high altitude exposure 1
• Pregnancy should be avoided due to high mortality risk 1
• Supervised exercise training for deconditioned patients 1
• Immunizations against influenza and pneumococcal pneumonia 1
• Incorporate palliative care services to address symptom burden 1

Special Considerations

• Treat supraventricular tachyarrhythmias aggressively 1
• Anticoagulation with warfarin for IPAH patients and those with indwelling catheters 1
• Management should occur at specialized centers with expertise in pulmonary hypertension 1

Common Pitfalls to Avoid

1. Using calcium channel blockers in non-vasoreactive PAH patients
2. Combining riociguat with PDE5i (severe hypotension risk)
3. Abrupt withdrawal of prostacyclin therapy
4. Delaying referral to specialized centers for advanced therapies
5. Missing regular monitoring assessments
6. Treating symptoms without addressing the underlying cause of PH

Early referral to specialized centers is critical for patients with inadequate response to therapy, high-risk features, or when considering surgical options 1.