What are the medication options for treating pulmonary hypertension?

Medication Options for Pulmonary Hypertension

The primary medication classes for treating pulmonary hypertension include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, prostacyclin pathway agents, and calcium channel blockers, with treatment selection based on WHO functional class and vasoreactivity testing.

Classification-Based Treatment Approach

Initial Assessment

• Vasoreactivity testing is essential for determining if calcium channel blockers are appropriate
• Risk stratification based on WHO functional class (I-IV), 6-minute walk distance, right ventricular function, and BNP/NT-proBNP levels 1

First-Line Medication Options

For Vasoreactive Patients (approximately 10% of IPAH)

• Calcium channel blockers (CCBs): nifedipine, diltiazem, or amlodipine 1
  • Only appropriate for the small subset of patients who demonstrate vasoreactivity

For Non-vasoreactive Patients

WHO Functional Class II-III

• Initial combination therapy preferred: ERA + PDE5I 1
  • Endothelin receptor antagonists (ERAs):
    • Bosentan: 62.5 mg twice daily for 4 weeks, then 125 mg twice daily 2, 3
    • Ambrisentan
    • Macitentan
  • Phosphodiesterase-5 inhibitors (PDE5Is):
    • Sildenafil: 20 mg three times daily 1, 4
    • Tadalafil: 40 mg once daily 1, 5
  • Soluble guanylate cyclase stimulator:
    • Riociguat 1

WHO Functional Class IV (High Risk)

• Intravenous prostacyclin analogs (first choice) 1
  • Epoprostenol (IV): First-line for severe disease 2
  • Treprostinil (IV, SC, inhaled): Alternative option 2
  • Iloprost (inhaled)

Sequential Combination Therapy

For patients with inadequate response to initial therapy:

• Add a second drug class if on monotherapy
• Add a third drug class (such as inhaled treprostinil, inhaled iloprost, or riociguat) if on dual therapy 1
• Consider oral selexipag as an additional option 1

Important Drug Interactions

Critical Interactions to Avoid

• PDE5Is (sildenafil/tadalafil) + nitrates: Contraindicated due to risk of profound hypotension 2, 4, 5
• Bosentan + cyclosporine: Contraindicated (bosentan levels increase 4-fold) 2
• Bosentan + glibenclamide: Contraindicated (increased aminotransferases) 2
• Sitaxentan + cyclosporine: Contraindicated (increases sitaxentan levels) 2

Interactions Requiring Dose Adjustments

• Bosentan + sildenafil: Sildenafil levels decrease by 50%, bosentan levels increase by 50% 2, 6
• Bosentan + warfarin: May need warfarin dose adjustment due to increased metabolism 2
• Sildenafil + HIV protease inhibitors: Sildenafil dose adjustments usually required 2

Monitoring Requirements

• For ERAs (especially bosentan): Regular liver function monitoring 1
• For all therapies: Regular assessment of:
  • WHO functional class
  • 6-minute walk distance
  • Right ventricular function
  • BNP/NT-proBNP levels 1

Special Considerations

• Pregnancy: Contraindicated in PAH patients (30-50% mortality risk) 1
• Hormonal contraceptives: May be unreliable with bosentan due to drug interactions 2
• Surgery: Non-essential surgery should be avoided; when necessary, care should be provided at a pulmonary hypertension center 1
• Air travel: Supplemental oxygen recommended to maintain saturations above 91% 1

Treatment Algorithm Based on Risk Assessment

Risk Category	Estimated 1-Year Mortality	Treatment Approach
Low Risk (<5%)	WHO FC I-II, 6MWD >440m	Initial oral combination therapy (ERA + PDE5I)
Intermediate Risk (5-10%)	WHO FC III, 6MWD 165-440m	Initial oral combination therapy or consider prostanoid-based therapy
High Risk (>10%)	WHO FC IV, 6MWD <165m	IV prostacyclin analog (epoprostenol) as cornerstone of therapy

Patients should be managed at specialized pulmonary hypertension centers with expertise in diagnosis and treatment, including regular comprehensive assessments to guide therapy adjustments 1.