Low-Molecular-Weight Heparin vs Warfarin for Thromboprophylaxis in Children With Coronary Artery Aneurysms After Kawasaki Disease: A Pragmatic Registry Trial

International Kawasaki Disease Registry

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3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1598-1607
Number of pages10
JournalCanadian Journal of Cardiology
Volume36
Issue number10
DOIs
StatePublished - Oct 2020

Bibliographical note

Funding Information:
The International Kawasaki Disease Registry (IKDR) is grateful for the hard work of the multiple research coordinators, research nurses, and students who collected the data for this registry across all participating centers. The IKDR specifically thanks Annette L. Baker (Boston Children's Hospital), Tanveer Collins (Hospital for Sick Children, Toronto), Amy Cooper (Nationwide Children's Hospital, Columbus, OH), Catherine Dimes (Nationwide Children's Hospital, Columbus, OH), Anne Fournier (Centre Hospitalier Universitaire Ste-Justine, Montr?al), David R. Fulton (Boston Children's Hospital), Sunita O'Shea (Hospital for Sick Children, Toronto), Mary Beth Son (Boston Children's Hospital), and Devin D. Thinker (Cincinnati Children's Hospital Medical Centre). Funding for the data coordinating centre was partially provided by the CIBC World Market Chair in Child Health Research (Brian McCrindle) and the Labatt Family Heart Centre at SickKids Hospital (Brian McCrindle). Additional local funding for participation in the International Kawasaki Disease Registry (IKDR) was provided by: les Fonds BoBeau Coeur of the Ste-Justine Hospital Foundation (Nagib Dahdah), the McCance Family Foundation (Jane Newburger), the Vella Fund (Jane Newburger) and the Children's Health Foundation of London, Ontario (Kambiz Norozi). J.W.N. is Chair of the Events Adjudication Committees for randomized trials by Bristol-Myers-Squibb and Pfizer on safety and efficacy of apixiban. The other authors have no conflicts of interest to disclose.

Funding Information:
Funding for the data coordinating centre was partially provided by the CIBC World Market Chair in Child Health Research (Brian McCrindle) and the Labatt Family Heart Centre at SickKids Hospital (Brian McCrindle). Additional local funding for participation in the International Kawasaki Disease Registry (IKDR) was provided by: les Fonds BoBeau Coeur of the Ste-Justine Hospital Foundation (Nagib Dahdah), the McCance Family Foundation (Jane Newburger), the Vella Fund (Jane Newburger) and the Children’s Health Foundation of London , Ontario (Kambiz Norozi).

Publisher Copyright:
© 2020 Canadian Cardiovascular Society

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