Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial
Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial
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DOI：
10.1016/s0140-6736(19)32518-8
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发表时间：
2019-12-21
期刊：
影响因子：
168.9
通讯作者：
Flather, Marcus
中科院分区：
文献类型：
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作者：
Mullen, Michael;Jin, Xu Yu;Flather, Marcus
背景：伊贝沙坦是一种长效的选择性血管紧张素受体拮抗剂，治疗马凡综合征可能会减少与夹层和破裂相关的主动脉扩张。我们的目标是确定厄贝沙坦对患有马凡综合征的儿童和成人的主动脉扩张率的影响。方法我们在英国的22个中心进行了一项安慰剂对照的双盲随机试验。6-40岁经临床确诊的马凡综合征患者有资格入选。研究参与者都被给予75毫克的开放标签厄贝沙坦，每天一次，然后随机分配到150毫克的厄贝沙坦(增加到300毫克的耐受性)或匹配的安慰剂。用超声心动图测量基础状态和每年的主动脉内径。所有的图像都由核心实验室分析，治疗分配是盲目的。主要终点是主动脉根部扩张率。这项试验在ISRCTN注册，编号为ISRCTN90011794。在2012年3月14日至2015年5月1日期间，192名参与者被招募并随机分配到厄贝沙坦组(n=104)或安慰剂组(n=88)，所有人都接受了长达5年的跟踪调查。招募时的中位年龄为18岁(IQR 12-28)，99名(52%)为女性，平均血压为110/65 mm Hg(SD16和12)，108名(56%)正在服用β-受体阻滞剂。厄贝沙坦组(SD 5.8)和安慰剂组(5.5)的平均基线主动脉根部直径为34.4 mm。厄贝沙坦组主动脉根部平均扩张速度为0.53 mm/年(95%可信区间0.39~0.67)，安慰剂组为0.74 mm/年(0.60~0.89)，差异有统计学意义(-0.22 mm/年，P=0.030)。伊贝沙坦也降低了主动脉Z积分的变化率(平均每年-0.10%，95%CI-0.19to-0.01，p=0.035)。伊贝沙坦耐受性良好，没有观察到严重不良事件发生率的差异。解释伊贝沙坦与降低患有马凡综合征的儿童和年轻人的主动脉扩张率有关，并可以降低主动脉并发症的发生率。版权所有(C)2019作者(S)。爱思唯尔有限公司出版。
Background Irbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome.Methods We did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6-40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794.Findings Between March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12-28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking beta blockers. Mean baseline aortic root diameter was 34.4 mm in the irbesartan group (SD 5.8) and placebo group (5.5). The mean rate of aortic root dilatation was 0.53 mm per year (95% CI 0.39 to 0.67) in the irbesartan group compared with 0.74 mm per year (0.60 to 0.89) in the placebo group, with a difference in means of -0.22 mm per year (-0.41 to -0.02, p=0.030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means -0.10 per year, 95% CI -0.19 to -0.01, p=0.035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events.Interpretation Irbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.