Weill Cornell & Institute of Academic Medicine, Houston Methodist Hospital, Houston Methodist Lung Center, Houston, Texas, USA.
Hannover Medical School and German Center of Lung Research (DZL), Hannover, Germany.
J Heart Lung Transplant. 2018 Dec;37(12):1410-1417. doi: 10.1016/j.healun.2018.07.001. Epub 2018 Sep 9.
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.
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.
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.
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.
多国 AMBITION 研究表明，与单药治疗相比，在初治的功能分级 II 和 III 肺动脉高压（PAH）患者中，起始联合治疗（安立生坦和他达拉非）可使首次临床失败事件（TtCF，死亡、因肺动脉高压恶化而住院、疾病进展或长期临床反应不佳的复合终点）的时间风险降低 50%。对 AMBITION 数据进行了基于基线 REVEAL 风险评分的风险分层后分析，以更好地评估联合治疗的影响。
患者按 2:1:1 的比例随机分配至起始联合治疗（安立生坦 10mg 加他达拉非 40mg）或各单药治疗加安慰剂。605 例患者的基线 REVEAL 风险评分分为低危、中危和高危。根据风险组和治疗分组评估确证结局（TtCF 和首次 PAH 住院或死亡的事后复合终点）。
基线时，各治疗组的风险组分布相似，低危（16%）、中危（46%）和高危（38%）。风险越高，结局越差。在每个风险水平，与单药治疗相比，联合治疗组 TtCF 或 PAH 住院/死亡事件明显减少，且联合治疗组因不良事件停药的发生率不高。
这项基于 REVEAL 风险组的事后分析显示，在 AMBITION 研究中，无论风险水平如何，接受起始联合治疗的患者都有更好的结局，甚至在被评估为低危的患者中，起始联合治疗也具有临床获益。
