Patients with pulmonary arterial hypertension with and without cardiovascular risk factors: Results from the AMBITION trial
Patients with pulmonary arterial hypertension with and without cardiovascular risk factors: Results from the AMBITION trial
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DOI：
10.1016/j.healun.2019.09.010
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发表时间：
2019-12-01
影响因子：
8.9
通讯作者：
Hoeper, Marius M.
中科院分区：
文献类型：
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作者：
McLaughlin, Vallerie V.;Vachiery, Jean-Luc;Hoeper, Marius M.
背景技术背景：本研究的目的是比较入组AMBITION试验的肺动脉高压患者与（从主要分析集[前主要分析集]中排除）和无（主要分析集）左心室舒张功能障碍的多个危险因素。初治的肺动脉高压患者随机接受安立生坦和他达拉非联合治疗、安立生坦单药治疗，或他达拉非单一疗法。主要终点是从随机化到首次判定临床失败事件的时间。结果：主要分析组患者（n = 500）与前主要分析组患者（n = 105）相比，更年轻（平均54.4 vs 62.1岁），基线6分钟步行距离更长（中位数363.7 vs 330.5米），合并症更少（例如，高血压和糖尿病）。初始联合治疗与汇总单药治疗的治疗效果在两个人群中方向相同，尽管前主要分析集患者的幅度较低。在主要分析集患者中，与汇总单药治疗相比，初始联合治疗降低了临床失败的风险（风险比，0.50; 95%置信区间，0.35-0.72），而在前主要分析集患者中效果不太明显（风险比，0.70; 95%置信区间，0.35-1.37）。总体而言，主要分析集患者的临床失败事件较少（25% vs 33%），满意临床缓解率更高（34% vs 24%），以及因不良事件而永久停用研究药物的发生率较低（16% vs 31%）高于前主要分析集患者。对于主要分析集和前主要分析集患者，初始联合治疗与汇总单药治疗的疗效在方向上相似。然而，前主要分析集患者（存在左心室舒张功能障碍的多种风险因素）的临床失败事件发生率更高，联合治疗与单药治疗相比的应答减弱。主要分析集患者的耐受性优于非主要分析集患者。(C)2019年国际心肺移植学会。All rights reserved.
BACKGROUND: The purpose of this study was to compare patients with pulmonary arterial hypertension enrolled in the AMBITION trial with (excluded from the primary analysis set [ex-primary analysis set]) and without (primary analysis set) multiple risk factors for left ventricular diastolic dysfunction.METHODS: Treatment-naive patients with pulmonary arterial hypertension were randomized to oncedaily ambrisentan and tadalafil combination therapy, ambrisentan monotherapy, or tadalafil monotherapy. The primary end point was time from randomization to first adjudicated clinical failure event.RESULTS: Primary analysis set patients (n = 500), compared with ex-primary analysis set patients (n = 105), were younger (mean, 54.4 vs 62.1 years) with greater baseline 6-minute walk distance (median, 363.7 vs 330.5 meters) and fewer comorbidities (e.g., hypertension and diabetes). Treatment effects of initial combination therapy vs pooled monotherapy were directionally the same for both populations, albeit of a lower magnitude for ex-primary analysis set patients. Initial combination therapy reduced the risk of clinical failure compared with pooled monotherapy in primary analysis set patients (hazard ratio, 0.50; 95% confidence interval, 0.35-0.72), whereas the effect was less clear in ex-primary analysis set patients (hazard ratio, 0.70; 95% confidence interval, 0.35-1.37). Overall, primary analysis set patients had fewer clinical failure events (25% vs 33%), higher rates of satisfactory clinical response (34% vs 24%), and lower rates of permanent study drug withdrawal due to adverse events (16% vs 31%) than ex-primary analysis set patients.CONCLUSIONS: Efficacy of initial combination therapy vs pooled monotherapy was directionally similar for primary analysis set and ex-primary analysis set patients. However, ex-primary analysis set patients (with multiple risk factors for left ventricular diastolic dysfunction) experienced higher rates of clinical failure events and the response to combination therapy vs monotherapy was attenuated. Tolerability was better in primary analysis set than ex-primary analysis set patients. (C) 2019 International Society for Heart and Lung Transplantation. All rights reserved.