What are the treatment options for pulmonary hypertension?

Treatment Options for Pulmonary Hypertension

Initial Assessment: Vasoreactivity Testing and Risk Stratification

All patients with suspected pulmonary arterial hypertension (PAH) must undergo vasoreactivity testing during right heart catheterization to determine treatment strategy. 1, 2

• Risk stratification using WHO functional class, exercise capacity (6-minute walk distance), echocardiographic findings, BNP/NT-proBNP levels, and hemodynamic parameters is essential before initiating therapy 1, 2
• Only approximately 10% of idiopathic PAH patients demonstrate acute vasoreactivity and qualify for calcium channel blocker therapy 2, 3

Treatment Algorithm Based on Vasoreactivity and Risk Status

For Vasoreactive Patients (IPAH, Heritable PAH, Drug-Induced PAH Only)

High-dose calcium channel blockers (long-acting nifedipine, diltiazem, or amlodipine) are the recommended first-line treatment for vasoreactive patients. 1, 2

• Verapamil should be avoided due to negative inotropic effects 2
• Patients must be closely monitored and if they fail to improve to WHO functional class I or II, additional PAH-specific therapy should be added 2

For Non-Vasoreactive Patients: Treatment by Risk Category

Low or Intermediate Risk (WHO FC II-III)

Initial oral combination therapy with ambrisentan plus tadalafil is recommended as first-line treatment, as it has proven superior to monotherapy in delaying clinical failure. 1, 2

• This combination demonstrated superiority in head-to-head comparison trials and should be prioritized over initial monotherapy 1
• If combination therapy is not tolerated, monotherapy options include endothelin receptor antagonists (bosentan, ambrisentan, macitentan) or phosphodiesterase-5 inhibitors (sildenafil 20mg three times daily, tadalafil 40mg once daily) 2, 4

High Risk (WHO FC IV)

Continuous intravenous epoprostenol should be prioritized as it is the only treatment proven to reduce 3-month mortality in high-risk PAH patients. 1, 2

• Initial combination therapy including intravenous prostacyclin analogues is recommended for all high-risk patients 1, 2
• Alternative prostacyclin analogues may be considered if intravenous epoprostenol is not feasible 1

Sequential Combination Therapy for Inadequate Response

If patients show inadequate clinical response to initial therapy (defined by worsening WHO functional class, declining 6-minute walk distance >15%, or rising BNP/NT-proBNP), sequential double or triple combination therapy is recommended. 1

• The combination of riociguat and PDE-5 inhibitors is absolutely contraindicated due to risk of severe hypotension 2
• Triple combination therapy should be attempted before considering lung transplantation 1
• Eligibility for lung transplantation should be considered after inadequate response to initial therapy, with referral soon after inadequate response on maximal combination therapy 1, 2

Supportive Measures (Essential for All Patients)

Diuretic treatment is indicated in all PAH patients with signs of right ventricular failure and fluid retention. 2

• Continuous long-term oxygen therapy is indicated when arterial blood oxygen pressure is consistently <8 kPa (60 mmHg) or oxygen saturations <90% 2
• Oral anticoagulation should be considered in patients with idiopathic PAH, heritable PAH, and PAH due to anorexigens 2, 3
• Supervised exercise rehabilitation should be considered for physically deconditioned patients already on medical therapy 2
• Immunization against influenza and pneumococcal pneumonia is recommended 2, 3
• Pregnancy is absolutely contraindicated due to 30-50% maternal mortality risk 2

Advanced and Rescue Therapies

Lung transplantation should be listed soon after inadequate clinical response is confirmed on maximal combination therapy. 1, 2

• Balloon atrial septostomy may be considered as a palliative or bridging procedure in patients deteriorating despite maximal medical therapy 1, 2
• Early consultation with a pulmonary hypertension specialist and transfer to a tertiary care center is advised for patients requiring advanced interventions 5

Critical Pitfalls to Avoid

• Never use PAH-specific therapies for Group 2 PH (left heart disease) - treatment should focus on optimizing the underlying cardiac condition 2
• Never combine riociguat with PDE-5 inhibitors - this combination is contraindicated 2
• Never delay referral to specialized centers - all PAH patients should be managed at centers with pulmonary hypertension expertise 2
• Never use verapamil as a calcium channel blocker in PAH due to negative inotropic effects 2
• Never avoid intubation solely due to PAH if clinically necessary, though recognize it carries increased risk and vasopressors/inotropes are preferred over fluid boluses in shock 5

Monitoring and Treatment Goals

• Regular follow-up every 3-6 months for stable patients, more frequently for advanced disease 2
• Treatment goals include achieving WHO functional class I or II and 6-minute walk distance >440m 2
• Patients on prostacyclin therapy may rapidly develop right ventricular failure and death if these medications are interrupted 5