Can I add ambrisentan to a patient with pulmonary artery hypertension on tadalafil, with persistent hypotension and a right-to-left shunt, but normal lactate levels and improving renal function?

Management of Hypotensive PAH Patient on Tadalafil: Adding Ambrisentan

Adding ambrisentan to a hypotensive PAH patient already on tadalafil is not recommended when systolic blood pressure remains below 90 mmHg, despite normal lactate and improving renal function.

Rationale for This Recommendation

Hemodynamic Considerations

• Persistent hypotension (SBP <90 mmHg) represents a significant risk for clinical deterioration, especially in a patient with a right-to-left shunt 1
• Adding ambrisentan, an endothelin receptor antagonist (ERA), could further lower systemic blood pressure and potentially worsen tissue perfusion 2
• The presence of a right-to-left shunt indicates severe disease with potential for worsening hypoxemia if vasodilation increases shunting 1

Evidence-Based Approach

Current guidelines recommend:

• Careful hemodynamic monitoring when adding or escalating PAH therapies 1
• Prioritizing hemodynamic stability before escalating therapy 2
• Avoiding treatments that may exacerbate hypotension in already compromised patients 2

Alternative Management Strategies

For the Current Hypotensive State:

1. Optimize volume status:

   • Careful fluid management to support blood pressure without overloading the right ventricle
   • Monitor urine output closely despite current improvement in renal function

2. Consider inotropic support if hypotension persists despite adequate volume status:

   • Low-dose dobutamine or milrinone may help improve cardiac output
   • Target improved systemic perfusion while monitoring for arrhythmias

3. Optimize current tadalafil therapy:

   • Ensure appropriate dosing based on renal function
   • Consider temporary dose reduction if contributing to hypotension

Once Blood Pressure Stabilizes (SBP >90 mmHg):

1. Reassess for combination therapy:

   • The combination of ambrisentan and tadalafil has shown significant benefits in PAH patients 1, 2
   • Guideline recommendation #71: "For stable or symptomatic PAH patients on background therapy with ambrisentan, we suggest the addition of tadalafil to improve 6MWD" 1
   • Note this is the reverse sequence of what you're considering

2. Consider prostacyclin pathway agents instead of ambrisentan if hypotension persists:

   • Inhaled prostacyclins may provide pulmonary selectivity with less systemic hypotension
   • "In patients with PAH who remain symptomatic on stable doses of an ERA or a PDE5I, we suggest the addition of inhaled iloprost" 1

Special Considerations for Right-to-Left Shunt

• Right-to-left shunting indicates severe disease with risk of worsening hypoxemia
• Monitor oxygen saturation closely if any vasodilator therapy is adjusted
• Supplemental oxygen should be used as needed to maintain saturations >91% 1
• Consider specialized PAH center referral if not already at one: "Such patients are ideally evaluated at centers with expertise in the evaluation and treatment of patients with PAH" 1

Monitoring Recommendations

If hemodynamics stabilize and ambrisentan is later added:

• Close monitoring of blood pressure for first 24-48 hours
• Daily assessment of renal function and fluid status
• Monitoring for signs of worsening right heart failure
• Regular assessment of oxygen saturation and shunt physiology

Key Pitfalls to Avoid

1. Adding vasodilators during hemodynamic instability can precipitate cardiovascular collapse
2. Excessive fluid administration can worsen right heart failure and pleural effusions 2
3. Delayed escalation of appropriate therapy once hemodynamically stable can lead to poor outcomes 2
4. Failure to refer to specialized centers for complex PAH management 2