The Safety and Effects of Bosentan in Patients with a Fontan Circulation
The Safety and Effects of Bosentan in Patients with a Fontan Circulation
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DOI：
10.1111/j.1747-0803.2012.00635.x
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发表时间：
2012-05-01
影响因子：
0.3
通讯作者：
Clift, Paul F.
中科院分区：
文献类型：
--
作者：
Bowater, Sarah E.;Weaver, Rebekah A.;Clift, Paul F.
Objective. Fontan循环的成年患者往往运动能力下降。本研究的主要目的是研究内皮素受体拮抗剂波生坦在Fontan患者中的安全性，其次是评估对心血管功能、纽约心脏协会功能分级（NYHA FC）和心室功能的影响。设计波生坦在Fontan患者中的6个月前瞻性、单中心、初探性、安全性研究。设置.成人先天性心脏病转诊中心。患者邀请所有≥ 18岁的Fontan循环患者和NYHA FC =II的患者入组。干预。患者开始接受62.5 mg bid波生坦，2周后上调至125 mg bid。结果衡量标准。通过6个月研究期间预期和非预期不良事件的发生率评估安全性;特别是通过每月血液检查测量的与肝、肾或血液功能障碍相关的不良事件。其他结局指标包括心肺运动试验、6分钟步行距离试验、博格呼吸困难指数、NYHA FC和经胸超声心动图心室功能参数。结果在入组的8名患者中，6名完成了研究。2例患者退出研究（1例因非试验相关原因，1例因不良事件）。本研究期间未发生与波生坦治疗相关的具有临床意义的不良事件，特别是未观察到肝功能检查的显著异常。3例患者报告了一过性不良事件。波生坦治疗6个月后，观察到NYHA FC和收缩心室功能改善。结论.在我们的研究中，少数Fontan循环患者能够耐受波生坦6个月。波生坦在更大患者人群中的安全性和耐受性仍未知。这里给出的结果证明了在更大的研究中进一步调查的合理性。
Objective. Adult patients with a Fontan circulation tend to have diminished exercise capacity. The principal objective of this study was to investigate the safety of the endothelin receptor antagonist bosentan in Fontan patients, and, secondarily, to assess effects on cardiovascular performance, New York Heart Association functional classification (NYHA FC), and ventricular function. Design. A 6-month prospective, single-center, pilot, safety study of bosentan in Fontan patients. Setting. Adult Congenital Heart Disease referral center. Patients. All patients =18 years old with a Fontan circulation and in NYHA FC =II were invited to enroll. Interventions. Patients started on 62.5 mg bid of bosentan, uptitrating to 125 mg bid after 2 weeks. Outcome Measures. Safety was assessed by the incidence of anticipated and unanticipated adverse events during the 6-month study period; specifically those relating to hepatic, renal, or hematological dysfunction as measured by monthly blood tests. Other outcome measures included cardiopulmonary exercise test, 6-minute walk distance test, Borg dyspnea index, NYHA FC, and ventricular function parameters using transthoracic echocardiography. Results. Of the eight patients enrolled, six completed the study. Two patients withdrew from the study (one for nontrial related reasons, one due to adverse events). No clinically significant adverse events relating to bosentan therapy occurred during this study and, in particular, no significant abnormalities in hepatic function tests were observed. Three patients reported transient adverse events. Improvements in NYHA FC and systolic ventricular function were observed after 6 months of bosentan treatment. Conclusions. The small number of patients with a Fontan circulation in our study was able to tolerate bosentan for 6 months. The safety and tolerability of bosentan in a larger patient population remains unknown. The results presented here justify further investigation in larger studies.