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首页> 外文期刊>The American Journal of Cardiology >Effectiveness of spironolactone plus ambrisentan for treatment of pulmonary arterial hypertension (from the [ARIES] Study 1 and 2 Trials)
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Effectiveness of spironolactone plus ambrisentan for treatment of pulmonary arterial hypertension (from the [ARIES] Study 1 and 2 Trials)

机译：螺内酯加安贝生坦治疗肺动脉高压的有效性（来自[ARIES]研究1和2试验）

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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 + 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.
机译：在肺动脉高压（PAH）的转化模型中，螺内酯可通过减轻醛固酮过多症对肺内皮细胞B型内皮素功能的不良影响来改善心肺血流动力学。该观察结果表明，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。我们检查了随机分组接受安慰剂或A型选择性内皮素受体拮抗剂安布森坦（10毫克/天）的患者的临床数据，其中ARIES-1和-2期间曾报告使用螺内酯，这些患者是随机，双盲，安慰剂-对照试验评估安布森坦对PAH临床疗效12周的影响。从随机分配给安慰剂（n = 132）或安布森坦（n = 67）的患者中，我们分别确定21例（15.9％）和10例（14.9％）患者同时使用螺内酯。与仅使用安贝生坦治疗的患者（n = 57）相比，安贝生坦+螺内酯治疗在第12周时的6分钟步行距离变化改善了94％（平均值±SE，+ 38.2±8.1 vs +74.2±27.4 m，p = 0.11）可使血浆B型利钠肽浓度提高1.7倍（p = 0.08），并使≥1世界卫生组织功能等级的患者人数相对增加90％（p = 0.08）。接受安贝森坦治疗的患者中，进行性疾病，PAH相关的住院治疗或死亡发生率为5.3％。然而，没有使用安贝生坦+螺内酯治疗的患者达到上述任何终点。总之，这些初步数据表明，螺内酯与内皮素A型受体拮抗作用在PAH中可能具有临床益处。需要进一步的临床试验来进一步表征我们的发现。

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