How to safely wean a patient with pulmonary arterial hypertension (PAH) off Veletri (epoprostenol)?

Weaning Veletri (Epoprostenol) in Pulmonary Arterial Hypertension

Critical Warning: Avoid Abrupt Withdrawal

Abrupt withdrawal or sudden large dose reductions of epoprostenol can result in rebound pulmonary hypertension with dyspnea, dizziness, and asthenia, and has been associated with death in PAH patients. 1

When Weaning May Be Considered

Weaning epoprostenol should only be attempted in highly selected patients who meet ALL of the following criteria:

• Persistent improvement in clinical and hemodynamic status 2
• Stable epoprostenol dose for at least 3 months 2
• Patient preference for oral therapy after thorough risk-benefit discussion 2
• Specific PAH etiologies with better prognosis: portopulmonary hypertension or HIV-associated PAH (these patients had higher success rates in published case series) 2
• Shorter duration of epoprostenol therapy (successful transitions occurred in patients treated for approximately 35 months vs. 79 months in those with partial success) 2
• Lower epoprostenol doses (approximately 15 ng/kg/min vs. 24 ng/kg/min in partial responders) 2

Specific Clinical Scenarios Where Weaning Has Been Reported

Post-Liver Transplantation in Portopulmonary Hypertension

In select patients with portopulmonary hypertension who undergo successful liver transplantation, gradual weaning may be possible, particularly in those with high cardiac output pre-transplantation that normalizes post-transplant. 3

• Monitor closely for increasing dyspnea, fluid retention, or fatigue during and after the wean 3
• Reinstitute epoprostenol immediately if symptoms recur 3

Weaning Protocol

Step 1: Pre-Weaning Assessment

• Confirm WHO Functional Class I-II status 2
• Document hemodynamic improvement with right heart catheterization 2
• Ensure stable or improving 6-minute walk distance (ideally >440 meters) 4
• Verify normal or near-normal BNP/NT-proBNP levels 5

Step 2: Initiate Replacement Therapy BEFORE Weaning

• Start oral PAH-specific therapy at therapeutic doses before reducing epoprostenol 3
• Consider phosphodiesterase-5 inhibitors (sildenafil or tadalafil) as replacement 3
• Alternative options include endothelin receptor antagonists or combination oral therapy 3
• Allow 2-4 weeks for oral therapy to reach steady state before beginning epoprostenol reduction 3

Step 3: Gradual Dose Reduction

• Reduce epoprostenol dose by no more than 1-2 ng/kg/min every 1-2 weeks 3
• Perform this under close observation, ideally in a specialized pulmonary hypertension center 3
• Monitor standing and supine blood pressure and heart rate for several hours after each dose reduction 1

Step 4: Intensive Monitoring During Weaning

• Assess clinical status weekly during active weaning 3
• Monitor for symptoms of rebound pulmonary hypertension: dyspnea, dizziness, asthenia, fluid retention, fatigue 3, 1
• Repeat 6-minute walk test every 2-4 weeks 2
• Check BNP/NT-proBNP levels every 2-4 weeks 5
• Perform repeat right heart catheterization if clinical deterioration occurs 2

Step 5: Post-Weaning Follow-Up

• Continue close monitoring for at least 3-6 months after complete discontinuation 3, 2
• Maintain all oral PAH therapies indefinitely 2
• Have a plan for rapid reinitiation of epoprostenol if needed 3

Expected Outcomes

In a small retrospective series of 8 highly selected patients:

• Complete successful transition (stable clinical and hemodynamic status): 50% of patients 2
• Partial successful transition (stable clinically but mild hemodynamic worsening without need to restart epoprostenol): 50% of patients 2
• All patients remained off epoprostenol during follow-up of 1.1 ± 0.5 years 2

Critical Pitfalls to Avoid

• Never attempt weaning in idiopathic or heritable PAH patients with severe disease or those requiring high epoprostenol doses (these patients typically require lifelong therapy) 3, 2
• Never reduce epoprostenol before establishing therapeutic levels of replacement oral therapy 3
• Never perform rapid dose reductions (this increases risk of rebound pulmonary hypertension and death) 1
• Never wean in outpatient settings without intensive monitoring capabilities 3
• Never attempt weaning in WHO Functional Class III-IV patients 2

When to Abort the Wean and Reinitiate Full-Dose Epoprostenol

Immediately return to previous stable epoprostenol dose if ANY of the following occur:

• Worsening WHO Functional Class 2
• Decrease in 6-minute walk distance >15% from baseline 2
• Rising BNP/NT-proBNP levels 5
• New or worsening symptoms: dyspnea, syncope, chest pain, edema 3, 1
• Hemodynamic deterioration on repeat catheterization 2