What is the treatment for group 1 pulmonary arterial hypertension?

Treatment for Group 1 Pulmonary Arterial Hypertension

The treatment of Group 1 pulmonary arterial hypertension requires a combination of specific pulmonary vasodilator medications targeting multiple pathways, with therapy selection based on WHO functional class and vasoreactivity testing.

Initial Assessment and Classification

• All patients with suspected pulmonary arterial hypertension (PAH) should undergo systematic evaluation using WHO functional class, exercise capacity, echocardiographic findings, laboratory values, and hemodynamic parameters to guide therapeutic decisions 1
• Vasoreactivity testing during right heart catheterization is essential to determine eligibility for calcium channel blocker therapy 2
• Risk assessment should include evaluation of family history, genetic mutations, and other conditions associated with increased PAH risk 2

Treatment Algorithm Based on Functional Class

WHO Functional Class I-II (Mild Symptoms)

• For vasoreactive patients with idiopathic PAH, calcium channel blockers (amlodipine, diltiazem, nifedipine) are recommended as first-line therapy 2
• For non-vasoreactive patients or those who fail CCB therapy, monotherapy with either endothelin receptor antagonists (ERAs), phosphodiesterase-5 inhibitors (PDE-5i), or soluble guanylate cyclase stimulators is recommended 1
• Ambrisentan is FDA-approved for PAH to improve exercise ability and delay clinical worsening in patients with WHO Functional Class II-III symptoms 3

WHO Functional Class III (Moderate Symptoms)

• Initial combination therapy with ambrisentan and tadalafil is recommended for treatment-naïve patients 1
• Bosentan has shown improvement in exercise capacity, functional class, hemodynamics, and time to clinical worsening in clinical trials 4
• Oral bosentan at 125 mg twice daily is the recommended target therapeutic dose, with monitoring of liver function required 4

WHO Functional Class IV (Severe Symptoms)

• Continuous intravenous epoprostenol, intravenous treprostinil, or subcutaneous treprostinil is strongly recommended 1
• Epoprostenol is FDA-approved for PAH to improve exercise capacity, particularly in patients with NYHA Functional Class III-IV symptoms 5
• Combination therapy targeting multiple pathways is recommended for these patients 6

Supportive and Preventive Measures

• Diuretics are indicated for PAH patients with signs of right ventricular failure and fluid retention 4, 1
• Supplemental oxygen should be used when arterial blood oxygen pressure is consistently <8 kPa (60 mmHg) to achieve an arterial blood oxygen pressure of >8 kPa for >15 h/day 4
• Anticoagulation should be considered, with target INR varying from 1.5-2.5 in North American centers to 2.0-3.0 in European centers 4, 2
• Patients should avoid going to altitudes above 1,500-2,000 m without supplemental oxygen 4
• Vaccination against influenza and pneumococcal pneumonia is recommended 4, 2
• Pregnancy is contraindicated in PAH due to 30-50% mortality risk 4

Combination Therapy Approach

• Current treatment consists of combination drug therapy targeting multiple biological pathways, which has shown demonstrable improvement in morbidity and mortality compared with single-pathway targeted monotherapy 7
• For patients who remain symptomatic on monotherapy, addition of a second class of medication is recommended 2
• Combination of bosentan and sildenafil has been shown to be safe and effective in improving exercise capacity, functional class, and hemodynamics 8

Monitoring and Follow-up

• Regular follow-up every 3-6 months for stable patients, more frequently for advanced disease 1
• Assessment should include functional class, exercise capacity tests (6-minute walk test), and echocardiographic evaluation 1
• Parameters indicating worse prognosis include clinical evidence of right ventricular failure, rapid progression of symptoms, syncope, WHO functional class IV, short 6-minute walk distance (<300m), elevated BNP/NT-proBNP levels, presence of pericardial effusion, and right atrial pressure >15 mmHg or cardiac index <2.0 L/min/m² 6

Advanced Options

• For patients with inadequate response to maximal medical therapy, lung transplantation should be considered 1
• Atrial septostomy may be considered as a palliative procedure or bridge to transplantation in selected cases 4
• Palliative care services should be incorporated for symptom management in advanced disease 1

Common Pitfalls and Caveats

• Delayed referral to specialized PH centers can result in inappropriate treatment and worse outcomes 1
• Inappropriate use of pulmonary vasodilator medications in patients with PH due to left heart disease can worsen outcomes 1
• Liver function monitoring is essential with bosentan therapy due to potential hepatotoxicity, with abnormal hepatic function occurring in approximately 10% of patients 4
• For patients requiring surgery during PAH exacerbation, care should be coordinated at a pulmonary hypertension center with careful monitoring of clinical status, oxygenation, and hemodynamics 6