低分子肝素与华法林预防川崎病后冠状动脉瘤患儿血栓形成的比较：一项实用登记试验。
Low-Molecular-Weight Heparin vs Warfarin for Thromboprophylaxis in Children With Coronary Artery Aneurysms After Kawasaki Disease: A Pragmatic Registry Trial.
机构信息
Division of Cardiology, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada.
Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
出版信息
Can J Cardiol. 2020 Oct;36(10):1598-1607. doi: 10.1016/j.cjca.2020.01.016. Epub 2020 Jul 1.
BACKGROUND
The substantial risk of thrombosis in large coronary artery aneurysms (CAAs) (maximum z-score ≥ 10) after Kawasaki disease (KD) mandates effective thromboprophylaxis. We sought to determine the effectiveness of anticoagulation (low-molecular-weight heparin [LMWH] or warfarin) for thromboprophylaxis in large CAAs.
METHODS
Data from 383 patients enrolled in the International KD Registry (IKDR) were used. Time-to-event analysis was used to account for differences in treatment duration and follow-up.
RESULTS
From diagnosis onward (96% received acetylsalicylic acid concomitantly), 114 patients received LMWH (median duration 6.2 months, interquartile range [IQR] 2.5-12.7), 80 warfarin (median duration 2.2 years, IQR 0.9-7.1), and 189 no anticoagulation. Cumulative incidence of coronary artery thrombosis with LMWH was 5.7 ± 3.0%, with warfarin 6.7 ± 3.7%, and with no anticoagulation 20.6 ± 3.0% (P < 0.001) at 2.5 years after the start of thromboprophylaxis (LMWH vs warfarin HR 1.5, 95% confidence interval [CI] 0.4-5.1; P = 0.56). A total of 51/63 patients with coronary artery thrombosis received secondary thromboprophylaxis (ie, thromboprophylaxis after a previous thrombus): 27 LMWH, 24 warfarin. There were no differences in incidence of further coronary artery thrombosis between strategies (HR 2.9, 95% CI 0.6-13.5; P = 0.19). Severe bleeding complications were generally rare (1.6 events per 100 patient-years) and were noted equally for patients on LMWH and warfarin (HR 2.3, 95% CI 0.6-8.9; P = 0.25).
CONCLUSIONS
LMWH and warfarin appear to have equivalent effectiveness for preventing thrombosis in large CAAs after KD, although event rates for secondary thromboprophylaxis and safety outcomes were low. Based on our findings, all patients with CAA z-score ≥ 10 should receive anticoagulation, but the choice of agent might be informed by secondary risk factors and patient preferences.
背景
川崎病（KD）后大冠状动脉瘤（CAA）（最大 z 评分≥10）存在明显的血栓形成风险，需要有效的血栓预防。我们旨在确定抗凝治疗（低分子肝素[LMWH]或华法林）对大 CAA 血栓预防的有效性。
方法
使用国际 KD 登记处（IKDR）纳入的 383 例患者的数据。采用生存分析来考虑治疗持续时间和随访时间的差异。
结果
从诊断开始（96%同时使用乙酰水杨酸），114 例患者接受 LMWH（中位持续时间 6.2 个月，四分位间距[IQR]2.5-12.7），80 例患者接受华法林（中位持续时间 2.2 年，IQR 0.9-7.1），189 例患者未接受抗凝治疗。接受 LMWH 的患者在开始抗栓治疗 2.5 年后的累积冠状动脉血栓形成发生率为 5.7%±3.0%，接受华法林的患者为 6.7%±3.7%，未接受抗凝治疗的患者为 20.6%±3.0%（P＜0.001）。LMWH 与华法林相比，冠状动脉血栓形成的 HR 为 1.5（95%CI 0.4-5.1；P=0.56）。共有 63 例冠状动脉血栓形成患者中的 51 例接受了二级抗栓治疗（即血栓形成前的抗栓治疗）：27 例 LMWH，24 例华法林。两种策略之间的进一步冠状动脉血栓形成发生率无差异（HR 2.9，95%CI 0.6-13.5；P=0.19）。严重出血并发症通常很少见（每 100 患者年发生 1.6 例），LMWH 和华法林患者的发生率相同（HR 2.3，95%CI 0.6-8.9；P=0.25）。
结论
LMWH 和华法林在预防 KD 后大 CAA 血栓形成方面似乎具有同等的疗效，尽管二级抗栓治疗和安全性结局的发生率较低。基于我们的发现，所有 CAA z 评分≥10 的患者均应接受抗凝治疗，但可根据次要危险因素和患者偏好选择药物。
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