Effectiveness of spironolactone plus ambrisentan for treatment of pulmonary arterial hypertension (from the [ARIES] study 1 and 2 trials).
Effectiveness of spironolactone plus ambrisentan for treatment of pulmonary arterial hypertension (from the [ARIES] study 1 and 2 trials).
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DOI：
10.1016/j.amjcard.2013.04.051
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发表时间：
2013-09-01
影响因子：
2.8
通讯作者：
Leopold, Jane A.
中科院分区：
文献类型：
--
作者：
Maron, Bradley A.;Waxman, Aaron B.;Opotowsky, Alexander R.;Gillies, Hunter;Blair, Christiana;Aghamohammadzadeh, Reza;Loscalzo, Joseph;Leopold, Jane A.
在肺动脉高压（PAH）转化模型中，螺内酯通过减轻醛固酮增多症对肺内皮细胞中内皮素B型受体功能的不良影响来改善心肺血流动力学。这一观察结果表明，将螺内酯与抑制内皮素A型受体介导的肺血管收缩相结合可能是PAH患者的一种有用的治疗策略。我们检查了随机接受安慰剂或选择性内皮素A型受体拮抗剂安立生坦（10 mg/天）的患者的临床数据，这些患者在ARIES-1和-2期间报告使用螺内酯，这是一项随机、双盲、安慰剂对照试验，评估了安立生坦治疗12周对PAH临床结局的影响。从随机分配至安慰剂组（n = 132）或安立生坦组（n = 67）的患者中，我们分别发现21例（15.9%）和10例（14.9%）患者同时使用螺内酯。与安立生坦单独治疗的患者（n = 57）相比，安立生坦D螺内酯治疗在第12周时使6分钟步行距离的变化改善了94%（平均值± SE，+38.2 ± 8.1 vs +74.2 ± 27.4 m，p = 0.11），血浆B型利钠肽浓度提高1.7倍（p = 0.08），并导致改善≥1个世界卫生组织功能分级的患者数量相对增加90%（p = 0.08）。5.3%的安贝生坦治疗患者的终点为疾病进展、PAH相关住院或死亡;然而，接受安贝生坦+螺内酯治疗的患者均未达到任何这些终点。总之，这些初步数据表明，螺内酯和内皮素A型受体拮抗剂联合治疗PAH可能具有临床获益。需要前瞻性临床试验来进一步表征我们的发现。
In translational models of pulmonary arterial hypertension (PAH), spironolactone improves cardiopulmonary hemodynamics by attenuating the adverse effects of hyperaldosteronism on endothelin type-B receptor function in pulmonary endothelial cells. This observation suggests that coupling spironolactone with inhibition of endothelin type-A receptor—mediated pulmonary vasoconstriction may be a useful treatment strategy for patients with PAH. We examined clinical data from patients randomized to placebo or the selective endothelin type-A receptor antagonist ambrisentan (10 mg/day) and in whom spironolactone use was reported during ARIES-1 and -2, which were randomized, double-blind, placebo-controlled trials assessing the effect of ambrisentan for 12 weeks on clinical outcome in PAH. From patients randomized to placebo (n = 132) or ambrisentan (n = 67), we identified concurrent spironolactone use in 21 (15.9%) and 10 (14.9%) patients, respectively. Compared with patients treated with ambrisentan alone (n = 57), therapy with ambrisentan D spironolactone improved change in 6-minute walk distance by 94% at week 12 (mean ± SE, +38.2 ± 8.1 vs +74.2 ± 27.4 m, p = 0.11), improved plasma B-type natriuretic peptide concentration by 1.7-fold (p = 0.08), and resulted in a 90% relative increase in the number of patients improving ≥1 World Health Organization functional class (p = 0.08). Progressive illness, PAH-associated hospitalizations, or death occurred as an end point for 5.3% of ambrisentan-treated patients; however, no patient treated with ambrisentan + spironolactone reached any of these end points. In conclusion, these pilot data suggest that coupling spironolactone and endothelin type-A receptor antagonism may be clinically beneficial in PAH. Prospective clinical trials are required to further characterize our findings.
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影响因子：
2.5
作者：
Elinoff JM;Rame JE;Forfia PR;Hall MK;Sun J;Gharib AM;Abd-Elmoniem K;Graninger G;Harper B;Danner RL;Solomon MA
通讯作者：
Solomon MA
影响因子：
37.8
作者：
Maron BA;Zhang YY;White K;Chan SY;Handy DE;Mahoney CE;Loscalzo J;Leopold JA
通讯作者：
Leopold JA
影响因子：
2.2
作者：
Bansal S;Badesch D;Bull T;Schrier RW
通讯作者：
Schrier RW
影响因子：
37.8
作者：
Piao L;Fang YH;Parikh KS;Ryan JJ;D'Souza KM;Theccanat T;Toth PT;Pogoriler J;Paul J;Blaxall BC;Akhter SA;Archer SL
通讯作者：
Archer SL
影响因子：
2.8
作者：
Krishnan, Usha;Takatsuki, Shinichi;Rosenzweig, Erika B.
通讯作者：
Rosenzweig, Erika B.