Risk-stratified outcomes with initial combination therapy in pulmonary arterial hypertension: Application of the REVEAL risk score

Adaani E. Frost, Marius M. Hoeper, Joan Albert Barberá, Jean Luc Vachiery, Christiana Blair, Jonathan Langley, Lewis J. Rubin

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


BACKGROUND: The multinational AMBITION study demonstrated a 50% risk reduction in time to first clinical failure event (TtCF, a composite of death, hospitalization for worsening pulmonary arterial hypertension [PAH], disease progression, or unsatisfactory long-term clinical response) in treatment-naive Functional Class II and III PAH patients initiated on combination therapy (ambrisentan and tadalafil) vs monotherapy. A post-hoc analysis of AMBITION data by risk stratification, as determined by baseline REVEAL risk score, was undertaken to better assess the impact of combination therapy. METHODS: Patients were randomized 2:1:1 to initial combination therapy with ambrisentan 10 mg plus tadalafil 40 mg vs either drug plus placebo, respectively. Baseline REVEAL risk scores in the 605 patients were grouped by low, intermediate, or high risk. Adjudicated outcomes (TtCF and post-hoc composite end-point of time to first PAH hospitalization or death) were assessed by risk group and treatment assignment. RESULTS: At baseline, risk groups were similarly represented across treatment assignments as low (16%), intermediate (46%), and high (38%) risk. Greater risk was associated with worse outcome. At each level of risk, patients on combination therapy had significantly fewer TtCF or PAH hospitalization/death events relative to those on monotherapy, and discontinuations due to adverse events were not higher on combination therapy. CONCLUSIONS: This post-hoc analysis comparing outcomes by REVEAL risk group has shown that, at all levels of risk, patients enrolled in AMBITION receiving initial combination therapy have superior outcomes and, even in those assessed as low risk, initial combination therapy was clinically beneficial.

Original languageEnglish (US)
Pages (from-to)1410-1417
Number of pages8
JournalJournal of Heart and Lung Transplantation
Issue number12
StatePublished - Dec 2018


  • REVEAL risk
  • ambrisentan
  • clinical research
  • combination therapy
  • pharmacotherapy
  • pulmonary hypertension
  • tadalafil

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation


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