安立生坦与他达拉非初始联合治疗结缔组织病相关肺动脉高压（CTD-PAH）：来自AMBITION试验的亚组分析
Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial.
作者信息
Coghlan John Gerry, Galiè Nazzareno, Barberà Joan Albert, Frost Adaani E, Ghofrani Hossein-Ardeschir, Hoeper Marius M, Kuwana Masataka, McLaughlin Vallerie V, Peacock Andrew J, Simonneau Gérald, Vachiéry Jean-Luc, Blair Christiana, Gillies Hunter, Miller Karen L, Harris Julia H N, Langley Jonathan, Rubin Lewis J
机构信息
Cardiology Department, Royal Free Hospital, London, UK.
Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, Bologna, Italy.
出版信息
Ann Rheum Dis. 2017 Jul;76(7):1219-1227. doi: 10.1136/annrheumdis-2016-210236. Epub 2016 Dec 30.
BACKGROUND
Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH.
OBJECTIVE
To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial.
METHODS
This was a post hoc analysis of patients with CTD-PAH and SSc-PAH from AMBITION, an event-driven, double-blind trial in patients with WHO functional class II/III PAH. Treatment-naive patients were randomised 2:1:1 to once-daily initial combination therapy with ambrisentan plus tadalafil or monotherapy with ambrisentan or tadalafil, respectively. The primary endpoint was time to the first clinical failure event (first occurrence of death, hospitalisation for worsening PAH, disease progression or unsatisfactory long-term clinical response).
RESULTS
In the primary analysis set (N=500), 187 patients had CTD-PAH, of whom 118 had SSc-PAH. Initial combination therapy reduced the risk of clinical failure versus pooled monotherapy in each subgroup: CTD-PAH (HR 0.43 (95% CI 0.24 to 0.77)) and SSc-PAH (0.44 (0.22 to 0.89)). The most common AE was peripheral oedema, which was reported more frequently with initial combination therapy than monotherapy in the two PAH subgroups. The relative frequency of adverse events between those on combination therapy versus monotherapy was similar across subgroups.
CONCLUSIONS
This post hoc subgroup analysis provides evidence that CTD-PAH and SSc-PAH patients benefit from initial ambrisentan and tadalafil combination therapy.
TRIAL REGISTRATION NUMBER
NCT01178073, post results.
背景
在大多数试验中，与特发性肺动脉高压（PAH）相比，结缔组织病相关肺动脉高压（CTD-PAH）患者，尤其是系统性硬化症（SSc）患者的反应减弱。因此，对于某些形式的CTD-PAH，PAH靶向治疗的益处存在不确定性。
目的
探讨在参加AMBITION试验的CTD-PAH和SSc-PAH患者中，安立生坦和他达拉非初始联合治疗与安立生坦或他达拉非单药治疗相比的安全性和有效性。
方法
这是一项对AMBITION试验中CTD-PAH和SSc-PAH患者的事后分析，该试验是一项针对WHO功能分级为II/III级PAH患者的事件驱动、双盲试验。初治患者按2:1:1随机分组，分别接受安立生坦加他达拉非每日一次的初始联合治疗或安立生坦或他达拉非单药治疗。主要终点是首次临床失败事件的时间（首次出现死亡、因PAH恶化住院、疾病进展或长期临床反应不满意）。
结果
在主要分析集（N=500）中，187例患者患有CTD-PAH，其中118例患有SSc-PAH。在每个亚组中，初始联合治疗与汇总的单药治疗相比降低了临床失败风险：CTD-PAH（风险比[HR]0.43[95%置信区间（CI）0.24至0.77]）和SSc-PAH（0.44[0.22至0.89]）。最常见的不良事件是外周水肿，在两个PAH亚组中，初始联合治疗组报告外周水肿的频率高于单药治疗组。联合治疗组与单药治疗组之间不良事件的相对频率在各亚组中相似。
结论
这项事后亚组分析提供了证据，表明CTD-PAH和SSc-PAH患者可从初始安立生坦和他达拉非联合治疗中获益。
试验注册号
NCT01178073，公布结果。
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