Sadeghipour Parham, Saedi Sedigheh, Saneei Leila, Rafiee Farnaz, Yoosefi Siamak, Parsaee Mozhgan, Siami Rashide, Saberi Milad, Pouraliakbar Hamidreza, Ghadrdoost Behshid, Bakhshandeh Hooman, Peighambari Mohammad Mehdi, Farrashi Melody, Mohebbi Bahram, Naderi Nasim, Amin Ahmad, Maleki Majid, Khajali Zahra, De Caterina Raffaele
Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
Clinical Trial Center, Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
Eur Heart J Cardiovasc Pharmacother. 2022 Sep 29;8(7):668-676. doi: 10.1093/ehjcvp/pvab083.
Thrombolysis is an alternative to surgery for mechanical prosthetic valve thrombosis (MPVT). Randomized clinical trials have yet to test the safety and efficacy of a proposed ultraslow thrombolytic infusion regimen.
This single-centre, open-label, pilot randomized clinical trial randomized adult patients with acute obstructive MPVT to an ultraslow thrombolytic regimen [25 mg of recombinant tissue-type plasminogen activator (rtPA) infused in 25 h] and a fast thrombolytic regimen (50 mg of rtPA infused in 6 h). If thrombolysis failed, a repeated dose of 25 mg of rtPA for 6 h was administered in both groups up to a cumulative dose of 150 mg or the occurrence of a complication. The primary outcome was a complete MPVT resolution (>75% fall in the obstructive gradient by transthoracic echocardiography, <10° limitation in opening and closing valve motion angles by fluoroscopy, and symptom improvement). The key safety outcome was a Bleeding Academic Research Consortium type III or V major bleeding. Overall, 120 patients, including 63 (52.5%) women, at a mean age of 36.3 ± 15.3 years, were randomized. Complete thrombolysis success was achieved in 51 patients (85.0%) in the ultraslow-regimen group and 47 patients (78.3%) in the fast-regimen group [odds ratio 1.58; 95% confidence interval (CI) 0.25-1.63; P = 0.34]. One case of transient ischaemic attack and three cases of intracranial haemorrhage (absolute risk difference -6.6%; 95%CI -12% -0.3%; P = 0.07) were observed only in the fast-regimen group.
The ultraslow thrombolytic regimen conferred a high thrombosis resolution rate without major complications. Such findings should be replicated in more adequately powered trials.
溶栓是治疗机械人工瓣膜血栓形成（MPVT）的一种替代手术的方法。随机临床试验尚未对拟议的超慢速溶栓输注方案的安全性和有效性进行测试。
这项单中心、开放标签的试点随机临床试验将急性梗阻性MPVT成年患者随机分为超慢速溶栓方案组（25小时内输注25mg重组组织型纤溶酶原激活剂（rtPA））和快速溶栓方案组（6小时内输注50mg rtPA）。如果溶栓失败，两组均给予25mg rtPA重复剂量，持续6小时，直至累积剂量达150mg或出现并发症。主要结局是MPVT完全溶解（经胸超声心动图显示梗阻梯度下降>75%，透视显示瓣膜开闭运动角度限制<10°，且症状改善）。关键安全结局是出血学术研究联盟III型或V型大出血。总体而言，120例患者被随机分组，其中包括63例（52.5%）女性，平均年龄为36.3±15.3岁。超慢速方案组51例患者（85.0%）和快速方案组47例患者（78.3%）实现了完全溶栓成功[比值比1.58；95%置信区间（CI）0.25 - 1.63；P = 0.34]。仅在快速方案组观察到1例短暂性脑缺血发作和3例颅内出血（绝对风险差异 - 6.6%；95%CI - 12% - 0.3%；P = 0.07）。
超慢速溶栓方案具有较高的血栓溶解率且无重大并发症。这些发现应在更具充分效力的试验中得到重复验证。
