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VascularClassic Trial Must Read⚡ High-Yield Board Topic

Initial Combination Therapy with Ambrisentan and Tadalafil in PAH (AMBITION)

Galiè N, Barberà JA, Frost AE et al.·New England Journal of Medicine·2015· DOI: 10.1056/NEJMoa1413687
PAHPulmonary HypertensionAmbrisentanTadalafilCombination TherapyERAPDE5i
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Background

Sequential add-on therapy was standard in PAH. AMBITION tested whether upfront combination therapy (ERA + PDE5i) was superior to monotherapy.

Study Design

Multicenter RCT (n=500) comparing upfront ambrisentan + tadalafil vs. ambrisentan alone or tadalafil alone in treatment-naive PAH patients.

Key Findings

Combination therapy reduced the risk of clinical failure events by 50% vs. pooled monotherapy (HR 0.50, p<0.001). Combination therapy also improved 6MWD, NT-proBNP, and WHO functional class.

Clinical Bottom Line

Upfront combination therapy (ERA + PDE5i) is now standard of care for newly diagnosed PAH. Ambrisentan + tadalafil is the best-studied combination. This trial changed PAH management from sequential to upfront combination therapy.

Limitations & Caveats

Open-label design. Pooled monotherapy comparator. Predominantly low-to-intermediate risk patients.

Faculty Notes— Dr. Andrew

This is THE trial that changed PAH management. Upfront dual combination = standard of care. Know the 50% risk reduction in clinical failure events.

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