Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial

Michael Mullen, Xu Yu Jin, Anne Child, et al

Lancet Published: December 10, 2019 DOI:https://doi.org/10.1016/S0140-6736(19)32518-8

Background 背景

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.

厄贝沙坦是一种长效的选择性血管紧张素-1受体阻滞剂，可能减少马凡综合征患者的主动脉扩张（主动脉扩张与夹层及破裂相关）。我们旨在确定厄贝沙坦对马凡综合征的儿童及成人主动脉扩张的影响。

Methods 方法

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.

我们在英国22个中心进行了一项安慰剂对照、双盲随机临床试验。临床确诊马凡综合征的6-40岁患者入选。所有患者均使用每日一次75 mg开放标签厄贝沙坦，然后随机分为厄贝沙坦150 mg（若耐受可加量至300 mg）或安慰剂。在基线及此后每年通过心脏超声检查测量主动脉直径。所有影像均由对试验分组设盲的中心实验室进行分析。主要预后终点为主动脉根部扩张率。试验在 ISRCTN 注册，注册号ISRCTN90011794。

Findings 结果

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 β 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.

2012年3月14日至2015年3月1日期间，共纳入192名患者，随机分为厄贝沙坦组(n=104)或安慰剂组(n=88)，所有患者均随访最长至5年。入选时中位年龄18 岁(IQR 12–28)，99名 (52%) 患者为女性，平均血压为 110/65 mm Hg (SDs 16 和 12)，108名 (56%) 患者使用 β 受体阻滞剂。厄贝沙坦组基线主动脉根部平均直径为 34·4 mm (SD 5·8)，安慰剂组 34·4 mm (5·5)。厄贝沙坦组主动脉根部扩张率平均为每年 0·53 mm (95% CI 0·39 to 0·67)，安慰剂组为 0·74 mm (0·60 to 0·89)，均值差异为每年 −0·22 mm (−0·41 to −0·02, p=0·030)。厄贝沙坦还能够降低主动脉Z评分改变率 (均值差异每年 −0·10, 95% CI −0·19 to −0·01, p=0·035)。厄贝沙坦耐受性良好，没有观察到严重不良事件发生率存在显著差异。

Interpretation 结论

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.

厄贝沙坦降低马凡综合征儿童及青年的主动脉扩张率，可以降低主动脉并发症的发生率。

Funding 资助

British Heart Foundation, the UK Marfan Trust, the UK Marfan Association.