TY - JOUR
T1 - Risk-stratified outcomes with initial combination therapy in pulmonary arterial hypertension
T2 - Application of the REVEAL risk score
AU - Frost, Adaani E.
AU - Hoeper, Marius M.
AU - Barberá, Joan Albert
AU - Vachiery, Jean Luc
AU - Blair, Christiana
AU - Langley, Jonathan
AU - Rubin, Lewis J.
N1 - Funding Information:
This study was sponsored by Gilead Sciences, Inc., and GlaxoSmithKline.
Publisher Copyright:
© 2018 International Society for Heart and Lung Transplantation
PY - 2018/12
Y1 - 2018/12
N2 - 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.
AB - 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.
KW - REVEAL risk
KW - ambrisentan
KW - clinical research
KW - combination therapy
KW - pharmacotherapy
KW - pulmonary hypertension
KW - tadalafil
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U2 - 10.1016/j.healun.2018.07.001
DO - 10.1016/j.healun.2018.07.001
M3 - Article
C2 - 30209017
AN - SCOPUS:85052989509
VL - 37
SP - 1410
EP - 1417
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
SN - 1053-2498
IS - 12
ER -