Atenolol versus losartan in children and young adults with Marfan's syndrome.
Atenolol versus losartan in children and young adults with Marfan's syndrome.
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DOI：
10.1056/nejmoa1404731
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发表时间：
2014-11-27
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影响因子：
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通讯作者：
Pediatric Heart Network Investigators
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作者：
Lacro RV;Dietz HC;Sleeper LA;Yetman AT;Bradley TJ;Colan SD;Pearson GD;Selamet Tierney ES;Levine JC;Atz AM;Benson DW;Braverman AC;Chen S;De Backer J;Gelb BD;Grossfeld PD;Klein GL;Lai WW;Liou A;Loeys BL;Markham LW;Olson AK;Paridon SM;Pemberton VL;Pierpont ME;Pyeritz RE;Radojewski E;Roman MJ;Sharkey AM;Stylianou MP;Wechsler SB;Young LT;Mahony L;Pediatric Heart Network Investigators
主动脉根部夹层是马凡氏综合征的主要死亡原因。研究表明，在减缓牙根扩大方面，氯沙坦可能比β受体阻滞剂更有效，β受体阻滞剂是目前大多数中心的标准治疗方法。我们进行了一项随机试验，比较氯沙坦与阿替洛尔治疗儿童和年轻成人马凡氏综合征。主要结果是牙根扩大率，表示为3年内以体表面积为指标的最大牙根直径z评分（以下简称牙根z评分）的变化。次要结果包括主动脉根部绝对直径的变化率;主动脉瓣返流的变化率;主动脉夹层、主动脉根部手术或死亡的时间;躯体生长;以及不良事件的发生率。从2007年1月至2011年2月，共有21个临床中心招募了608名年龄在6个月至25岁之间（平均[±SD]年龄，阿替洛尔组为11.5±6.5岁，氯沙坦组为11.0±6.2岁）的受试者，他们的astic-root z评分大于3.0。阿替洛尔组和氯沙坦组之间的基线校正的Z值变化率（±SE）无显著差异（分别为每年-0.139 ±0.013和-0.107 ±0.013标准差单位; P = 0.08）。两个斜率均显著小于零，表明两种治疗的牙根扩张程度相对于体表面积有所降低。两个治疗组之间的3年动脉根部手术、主动脉夹层、死亡和这些事件的复合发生率没有显著差异。在马凡氏综合征的儿童和年轻成人中，随机分配到氯沙坦或阿替洛尔组，我们发现两个治疗组在3年内的动脉根部扩张率没有显著差异。（由国家心肺血液研究所和其他机构资助; ClinicalTrials.gov编号，NCT 00429364。
Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events. From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [±SD] age, 11.5±6.5 years in the atenolol group and 11.0±6.2 years in the losartan group), who had an aortic-root z score greater than 3.0. The baseline-adjusted rate of change (±SE) in the aortic-root z score did not differ significantly between the atenolol group and the losartan group (−0.139±0.013 and −0.107±0.013 standard-deviation units per year, respectively; P = 0.08). Both slopes were significantly less than zero, indicating a decrease in the degree of aortic-root dilatation relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aortic-root dilatation between the two treatment groups over a 3-year period. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00429364.)