What are the treatment options for pulmonary hypertension?

Treatment Options for Pulmonary Arterial Hypertension

Initial Assessment and Vasoreactivity Testing

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

• Vasoreactivity testing uses inhaled nitric oxide, IV epoprostenol, or IV adenosine to identify the approximately 10% of patients who may respond to calcium channel blockers 3, 1
• A positive acute response is defined as a fall in mean pulmonary artery pressure of at least 10 mmHg to ≤40 mmHg, with increased or unchanged cardiac output 3
• Risk stratification using WHO functional class, exercise capacity (6-minute walk distance), echocardiographic findings, BNP/NT-proBNP levels, and hemodynamic parameters guides therapy intensity 1, 4

Treatment Algorithm Based on Vasoreactivity and Functional Class

For Vasoreactive Patients (WHO Functional Class I-III)

High-dose calcium channel blockers are the first-line treatment for vasoreactive patients with idiopathic PAH. 3, 1

• Use long-acting nifedipine, diltiazem, or amlodipine; avoid verapamil due to negative inotropic effects 1
• Patients must be closely monitored and if they fail to improve to functional class I or II within 3-6 months, additional PAH-specific therapy must be added 3, 1
• Sustained response is defined as patients remaining in NYHA functional class I or II with near-normal hemodynamics after several months of treatment 3

For Non-Vasoreactive Patients (WHO Functional Class II-III)

Initial oral combination therapy with ambrisentan (endothelin receptor antagonist) and tadalafil (phosphodiesterase-5 inhibitor) is the recommended first-line treatment. 1, 2

• This combination has proven superior to initial monotherapy in delaying clinical failure 1
• Sildenafil 20 mg three times daily (4-6 hours apart) is an alternative PDE-5 inhibitor option 5, 6
• Bosentan (dual endothelin receptor antagonist) 62.5 mg twice daily for 4 weeks, then 125 mg twice daily, improved 6-minute walk distance by 44 meters compared to placebo 7, 6

For High-Risk Patients (WHO Functional Class IV)

Continuous intravenous epoprostenol must be prioritized as first-line therapy for WHO Functional Class IV patients, as it is the only treatment proven to reduce mortality. 1, 8

• IV epoprostenol reduced 3-month mortality in high-risk PAH patients and improved 6-minute walk distance by 31-46 meters compared to conventional therapy 1, 6
• Initial combination therapy including IV prostacyclin analogues is recommended for high-risk patients 1
• Subcutaneous treprostinil is an alternative prostacyclin analogue, initiated at 1.25 ng/kg/min (or 0.625 ng/kg/min if not tolerated), with dose increases of 1.25 ng/kg/min per week for the first four weeks 9, 6

Supportive Measures

Diuretics are indicated for all PAH patients with signs of right ventricular failure and fluid retention. 1, 2

• Continuous long-term oxygen therapy is indicated when arterial blood oxygen pressure is consistently <8 kPa (60 mmHg) to maintain saturations >90% 1, 4
• Oral anticoagulation with warfarin should be considered in patients with idiopathic PAH, heritable PAH, and PAH due to anorexigens 3, 1, 2
• Supervised exercise rehabilitation should be considered for physically deconditioned patients on stable medical therapy 1
• Immunization against influenza and pneumococcal pneumonia is recommended 1, 2

Critical Contraindications and Drug Interactions

Never combine riociguat with PDE-5 inhibitors (sildenafil, tadalafil) due to risk of severe hypotension. 1

• Never use PAH-specific medications with nitrate medicines due to risk of life-threatening hypotension 5
• Pregnancy is absolutely contraindicated in PAH due to 30-50% maternal mortality risk 1, 2
• Avoid high altitude exposure or use supplemental oxygen during air travel to maintain oxygen saturations >91% 2

Advanced Therapies for Refractory Disease

Lung transplantation should be considered early after inadequate clinical response on maximal medical therapy. 1, 4

• Balloon atrial septostomy may be considered as a palliative or bridging procedure in patients deteriorating despite maximal medical therapy 1, 4
• Early consultation with a pulmonary hypertension specialist and transfer to a tertiary care center is advised for patients requiring invasive monitoring or mechanical support 10

Monitoring and Treatment Goals

Regular follow-up every 3-6 months for stable patients is required, with more frequent assessment for advanced disease. 1

• Treatment goals include achieving WHO functional class I or II and a 6-minute walk distance >440 meters 1
• Assessment should include functional class, 6-minute walk distance, echocardiographic evaluation of right ventricular function, and BNP/NT-proBNP levels 1, 4
• Avoid abrupt cessation of prostacyclin infusions as this can lead to rapid clinical deterioration and death 9, 10

Common Pitfalls

• Do not use PAH-specific therapies for Group 2 PH (left heart disease); instead, optimize the underlying cardiac condition 1, 4
• For Group 4 PH (chronic thromboembolic), pulmonary endarterectomy is the treatment of choice when feasible, not medical therapy 1, 4
• Intubation should be avoided if possible in PAH patients with right ventricular failure, as positive pressure ventilation can worsen right ventricular function 10
• Fluid boluses are often contraindicated in hypotensive PAH patients; vasopressors and inotropes are preferred to avoid exacerbating right ventricular ischemia 10