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

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.

• Authors: Cedric Manlhiot, Jane W Newburger, Tisiana Low, Nagib Dahdah, Andrew S Mackie, Geetha Raghuveer, Therese M Giglia, Frederic Dallaire, Mathew Mathew, Kyle Runeckles, Elfriede Pahl, Ashraf S Harahsheh, Kambiz Norozi, Sarah D de Ferranti, Kevin Friedman, Anji T Yetman, Shelby Kutty, Tapas Mondal, Brian W McCrindle, International Kawasaki Disease Registry
• Journal: The Canadian journal of cardiology (Can J Cardiol) Vol. 36 Issue 10 Pg. 1598-1607 (10 2020) ISSN: 1916-7075 [Electronic] England
• PMID: 32621885 (Publication Type: Journal Article, Multicenter Study, Observational Study, Pragmatic Clinical Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anticoagulants
• Heparin, Low-Molecular-Weight
• Warfarin

Topics

• Anticoagulants (administration & dosage, adverse effects)
• Canada (epidemiology)
• Chemoprevention (methods, statistics & numerical data)
• Child, Preschool
• Coronary Aneurysm (complications, drug therapy)
• Female
• Hemorrhage (chemically induced, epidemiology)
• Heparin, Low-Molecular-Weight (administration & dosage, adverse effects)
• Humans
• Incidence
• Male
• Mucocutaneous Lymph Node Syndrome (complications, epidemiology)
• Registries (statistics & numerical data)
• Risk Adjustment
• Thrombosis (epidemiology, etiology, prevention & control)
• United States (epidemiology)
• Warfarin (administration & dosage, adverse effects)