Department of Surgical Sciences, Vascular Surgery, Uppsala, Sweden.
Department of Surgical Sciences, Vascular Surgery, Uppsala, Sweden.
Eur J Vasc Endovasc Surg. 2021 Feb;61(2):326-331. doi: 10.1016/j.ejvs.2020.10.020. Epub 2020 Nov 20.
Vascular Ehlers-Danlos syndrome (vEDS) is a rare monogenetic disease caused by pathogenic variants in procollagen 3A1. Arterial rupture is the most serious clinical manifestation. A randomised controlled trial, the Beta-Blockers in Ehlers-Danlos Syndrome Treatment (BBEST) trial, reported a significant protective effect of the beta blocker celiprolol. The aim was to study the outcome of celiprolol treatment in a cohort of Swedish patients with vEDS.
Uppsala is a national referral centre for patients with vEDS. They are assessed by vascular surgeons, angiologists, and clinical geneticists. Family history, previous and future clinical events, medication, and side effects are registered. Celiprolol was administered twice daily and titrated up to a maximum dose of 400 mg daily. Logistic regression was used to analyse predictors of vascular events.
Forty patients with pathogenic sequence variants in COL3A1 were offered treatment with celiprolol in the period 2011-2019. The median follow up was 22 months (range 1-98 months); total follow up was 106 patient years. In two patients, uptitration of the dose is ongoing. Of the remaining 38, 26 (65%) patients reached the target dose of 400 mg daily. Dose uptitration was unsuccessful in six patients because of side effects; one died before reaching the maximum dose, and five terminated the treatment. Five major vascular events occurred; four were fatal (ruptured ascending aorta; aortic rupture after type B dissection; ruptured cerebral aneurysm; and ruptured pulmonary artery). One bled from a branch of the internal iliac artery, which was successfully coiled endovascularly. The annual risk of a major vascular event was 4.7% (n = 5/106), similar to the treatment arm of the BBEST trial (5%) and lower than in the control arm of the same trial (12%). No significant predictor of vascular events was identified.
Treatment with celiprolol is tolerated in most patients with vEDS. Despite fatal vascular events, these observations suggest that celiprolol may have a protective effect in vEDS.
血管型埃勒斯-当洛斯综合征（vEDS）是一种由前胶原 3A1 中的致病变异引起的罕见单基因疾病。动脉破裂是最严重的临床表现。一项随机对照试验，即贝塔阻断剂在埃勒斯-当洛斯综合征治疗中的作用（BBEST）试验，报告了β受体阻滞剂塞利洛尔的显著保护作用。目的是研究塞利洛尔治疗瑞典 vEDS 患者队列的结果。
乌普萨拉是 vEDS 患者的国家转诊中心。由血管外科医生、血管造影医生和临床遗传学家进行评估。家族史、既往和未来的临床事件、药物和副作用均有记录。塞利洛尔每天服用两次，并滴定至最大剂量 400mg/天。使用逻辑回归分析血管事件的预测因素。
2011 年至 2019 年期间，40 名 COL3A1 致病性序列变异患者接受了塞利洛尔治疗。中位随访时间为 22 个月（范围 1-98 个月）；总随访时间为 106 患者年。在两名患者中，剂量滴定仍在继续。在其余 38 名患者中，26 名（65%）患者达到了每日 400mg 的目标剂量。6 名患者因副作用而未能增加剂量；一名患者在达到最大剂量前死亡，五名患者终止了治疗。发生了 5 例重大血管事件；4 例是致命的（升主动脉破裂；B 型夹层后主动脉破裂；脑动脉瘤破裂；肺动脉破裂）。1 例髂内动脉分支出血，成功进行了血管内栓塞。每年发生重大血管事件的风险为 4.7%（n=106），与 BBEST 试验的治疗组（5%）相似，低于同一试验的对照组（12%）。未发现血管事件的显著预测因素。
大多数 vEDS 患者对塞利洛尔治疗耐受良好。尽管发生了致命的血管事件，但这些观察结果表明，塞利洛尔可能对 vEDS 具有保护作用。
