Tadalafil monotherapy and as add-on to background bosentan in patients with pulmonary arterial hypertension
Tadalafil monotherapy and as add-on to background bosentan in patients with pulmonary arterial hypertension
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DOI：
10.1016/j.healun.2010.11.009
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发表时间：
2011-06-01
影响因子：
8.9
通讯作者：
Galie, Nazzareno
中科院分区：
文献类型：
--
作者：
Barst, Robyn J.;Oudiz, Ronald J.;Galie, Nazzareno
背景：在一项为期16周的双盲安慰剂(PBO)对照试验中，他达拉非每天口服40毫克，被证明是耐受性良好的，对治疗肺动脉高压有效。纳入标准包括背景波森特人的选择。他达拉非在未接受治疗的患者中的分析以及作为波生坦的补充已预先指定。目的：提供两组的安全性和有效性数据。方法：分析组包括：治疗-NAIVE+PBO；治疗-NAIVE+他达拉非；背景波生坦+PBO；以及背景波生坦+他达拉非。随机接受他达拉非或PBO治疗的患者(N=405)按波生坦使用情况进行分析(YES=216，NO=189)。在6分钟步行距离(6MWD，PBO调整)、功能分级(FC)、临床恶化(CW)和不良事件方面评估治疗差异。结果：16周时，未接受治疗的患者他达拉非40 mg的6MWD增加44m(CI：20~69m；n=37)，加入波生坦40 mg的他达拉非增加23m(CI：-2~48m；n=42)。与基线相比，治疗初期和背景波生坦PBO患者在第16周的6MWD分别减少了3m和增加了19m。2例(5%)初治患者使用他达拉非40 mg进行CW，8例(22%)使用PBO(HR=3.3，CI：1.1~10.0)。2名(5%)背景波生坦患者接受了CW+他达拉非40 mg，而使用PBO+5例(11%)(HR=1.9，CI：0.4~10.2)。结论：他达拉非40 mg耐受性良好，可作为单用药对患者产生临床益处。当加入波生坦的背景时，它的耐受性也很好，但数据不足以得出额外的好处。J心肺移植杂志2011；30：632-43(C)2011国际心肺移植学会。版权所有。
BACKGROUND: Tadalafil 40 mg orally once daily, was shown to be well-tolerated and efficacious for pulmonary arterial hypertension in a 16-week, double-blind, placebo (PBO)-controlled trial. Inclusion criteria included the option for background bosentan. Analyses of tadalafil in treatment-naive patients and as add-on to bosentan were pre-specified. Objectives were to provide safety and efficacy data for both groups.METHODS: Groups analyzed included: treatment-naive + PBO; treatment-naive + tadalafil; background bosentan + PBO; and background bosentan + tadalafil. Patients randomized to tadalafil or PBO (N = 405) were analyzed by bosentan use (yes = 216, no = 189). Treatment differences in 6-minute walk distance (6MWD, PBO-adjusted), functional class (FC), clinical worsening (CW) and adverse events were assessed. Hazard ratios (HRs) with 95% confidence intervals (CIs) are presented for FC and CW.RESULTS: At Week 16, PBO-adjusted 6MWD increases were 44 m (CI: 20 to 69 m; n = 37) for tadalafil 40 mg in treatment-naive patients and 23 m (CI: -2 to 48 m; n = 42) for tadalafil 40 mg add-on to bosentan. The 6MWD for treatment-naive and background bosentan PBO patients decreased by 3 m and increased by 19 m, respectively, at Week 16 compared with baseline. Two (5%) treatment-naive patients had CW with tadalafil 40 mg vs 8 (22%) with PBO (HR = 3.3, CI: 1.1 to 10.0). Two (5%) background bosentan patients had CW with tadalafil 40 mg add-on vs 5 (11%) for PBO add-on (HR = 1.9, CI: 0.4 to 10.2). Adverse events for tadalafil monotherapy and as add-on were similar.CONCLUSION: Tadalafil 40 mg was well-tolerated and provided clinical benefit in patients as monotherapy. It was also well-tolerated when added to background bosentan, but data are insufficient to conclude additional benefit. J Heart Lung Transplant 2011;30:632-43 (C) 2011 International Society for Heart and Lung Transplantation. All rights reserved.