Anastrozole in Pulmonary Arterial Hypertension A Randomized, Double-Blind, Placebo-controlled Trial
Anastrozole in Pulmonary Arterial Hypertension A Randomized, Double-Blind, Placebo-controlled Trial
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DOI：
10.1164/rccm.201605-1024oc
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发表时间：
2017-02-01
影响因子：
24.7
通讯作者：
Ventetuolo, Corey E.
中科院分区：
文献类型：
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作者：
Kawut, Steven M.;Archer-Chicko, Christine L.;Ventetuolo, Corey E.
基本原理：芳香化酶抑制剂阿那曲唑可阻断雄激素向雌激素的转化，减轻动物的肺动脉高压，但其治疗肺动脉高压（PAH）患者的疗效尚不清楚。目的：我们旨在确定阿那曲唑治疗PAH的安全性和有效性。我们进行了一项随机，双盲，在两个中心接受背景治疗的PAH患者中进行的阿那曲唑安慰剂对照试验。测量和主要结果：共有18例PAH患者以2：1的比例随机接受阿那曲唑1 mg或匹配安慰剂治疗。两个共同主要结局是3个月时17 β-雌二醇水平（E2）和三尖瓣环平面收缩期偏移（TAPSE）较基线的百分比变化。与安慰剂相比，阿那曲唑显著降低了E2水平（百分比变化：-40%;四分位距[IQR]，-61至-26% vs. -4%; IQR，-14至+4%; P = 0.003），但TAPSE无差异。与安慰剂组（中位变化= -12 m）相比，阿那曲唑组显著增加了6分钟步行距离（中位变化= +26 m）（中位百分比变化：阿那曲唑组，8%; IQR，2 - 17% vs.安慰剂组-2%; IQR，-7至+1%; P = 0.042）。阿那曲唑对循环生物标志物、功能分类或健康相关生活质量无影响。阿那曲唑显著降低PAH患者的E2水平，但对TAPSE无影响。阿那曲唑是安全的，耐受性良好，并改善了6分钟步行距离在这个小的“原则证明”研究。可能需要在PAH患者中进行更大规模和更长时间的阿那曲唑II期临床试验。
Rationale: The aromatase inhibitor anastrozole blocks the conversion of androgens to estrogen and blunts pulmonary hypertension in animals, but its efficacy in treating patients with pulmonary arterial hypertension (PAH) is unknown.Objectives: We aimed to determine the safety and efficacy of anastrozole in PAH.Methods: We performed a randomized, double-blind, placebo controlled trial of anastrozole in patients with PAH who received background therapy at two centers.Measurements and Main Results: A total of 18 patients with PAH were randomized to anastrozole 1 mg or matching placebo in a 2:1 ratio. The two co-primary outcomes were percent change from baseline in 17 beta-estradiol levels (E2) and tricuspid annular plane systolic excursion (TAPSE) at 3 months. Anastrozole significantly reduced E2 levels compared with placebo (percent change: -40%; interquartile range [IQR], -61 to -26% vs. -4%; IQR, -14 to +4%; P = 0.003), but there was no difference in TAPSE. Anastrozole significantly increased the 6-minute-walk distance (median change = +26 m) compared with placebo (median change = -12 m) (median percent change: anastrozole group, 8%; IQR, 2 to 17% vs. placebo -2%; IQR, -7 to +1%; P = 0.042). Anastrozole had no effect on circulating biomarkers, functional class, or health-related quality of life. There was no difference in adverse events.Conclusions: Anastrozole significantly reduced E2 levels in patients with PAH but had no effect on TAPSE. Anastrozole was safe, well tolerated, and improved 6-minute-walk distance in this small "proof-of-principle" study. Larger and longer phase II clinical trials of anastrozole may be warranted in patients with PAH.