RCT

AMBITION

Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension

NEJM, 2015 · Multicenter double-blind randomized active-comparator trial (n=500)

Clinical question

Does upfront initial combination therapy with ambrisentan and tadalafil reduce clinical failure compared with monotherapy in treatment-naive PAH?

Population: Treatment-naive patients with WHO Functional Class II or III pulmonary arterial hypertension
Intervention: Combination therapy with ambrisentan (10 mg daily) plus tadalafil (40 mg daily)
Comparator: Pooled monotherapy with ambrisentan alone or tadalafil alone
Primary outcome: Time to first event of clinical failure (death, hospitalization for worsening PAH, disease progression, or unsatisfactory response)
Result: Clinical failure occurred in 18% of the combination-therapy group vs 31% of the pooled-monotherapy group (hazard ratio 0.50; 95% CI, 0.35 to 0.72; P<0.001). Hospitalizations for worsening PAH were reduced by 63% (P=0.002).

What the trial found

Initial upfront dual oral combination therapy halves the rate of clinical failure and hospitalization in treatment-naive pulmonary arterial hypertension.

Current guideline position

Supports initial combination therapy in appropriate PAH phenotypes within the ESC/ERS risk-based treatment framework; treatment selection is individualized by risk, comorbidity and PAH subtype.

Clinical interpretation

Established a strong evidence base for initial dual oral combination therapy in appropriately selected treatment-naive WHO functional class II-III PAH, while current therapy remains risk-stratified rather than universally identical for every patient.

Clinical Context & Relevant Topics (1)

Disease Reference

Pulmonary Hypertension & Acute Decompensation

Hemodynamic classification, right ventricular afterload reduction, selective pulmonary vasodilation, and pulmonary hypertensive crisis management.

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