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.
Résumé
Contexte
Le risque considérable de thrombose dans les cas de gros anévrismes coronariens (score
Z maximal ≥ 10) après une maladie de Kawasaki commande une thromboprophylaxie efficace.
Cette étude tentait de déterminer l’efficacité réelle de l’anticoagulothérapie (héparine
de bas poids moléculaire [HBPM] ou warfarine) en guise de thromboprophylaxie chez
les patients présentant de gros anévrismes coronariens.
Méthodologie
L’étude reposait sur les données recueillies auprès de 383 patients inscrits au registre
international de la maladie de Kawasaki. Une analyse du temps écoulé avant la survenue
de l’événement d’intérêt a été utilisée pour tenir compte des différences quant aux
périodes de traitement et de suivi.
Résultats
À partir du moment où ils ont reçu un diagnostic, 114 patients ont reçu une HBPM (durée
médiane du traitement : 6,2 mois; intervalle interquartile [IIQ] : 2,5-12,7), 80 patients
ont reçu de la warfarine (durée médiane du traitement : 2,2 ans; IIQ : 0,9-7,1), et
189 patients n’ont reçu aucune anticoagulothérapie (96 % des patients ont reçu de
l’acide acétylsalicylique en concomitance). Deux ans et demi après l’instauration
de la thromboprophylaxie, l’incidence cumulative des cas de thrombose coronarienne
était de 5,7 ± 3,0 % dans le groupe HBPM, de 6,7 ± 3,7 % dans le groupe warfarine
et de 20,6 ± 3,0 % dans le groupe ne recevant aucune anticoagulothérapie (p < 0,001) (rapport des risques instantanés [RRI], HBPM vs warfarine : 1,5; intervalle
de confiance [IC] à 95 % : 0,4-5,1; p = 0,56). Sur les 63 patients qui ont subi une thrombose coronarienne, 51 ont reçu
une thromboprophylaxie secondaire (c.-à-d. une thromboprophylaxie subséquente à une
thrombose) : 27 de ces patients ont reçu une HBPM et 24, de la warfarine. Aucune différence
n’a été observée entre les stratégies quant à la survenue d’une nouvelle thrombose
coronarienne (RRI : 2,9; IC à 95 % : 0,6-13,5; p = 0,19). Les complications hémorragiques graves étaient généralement rares (1,6 événement
par 100 années-patients) et sont survenues aussi bien dans le groupe HBPM que dans
le groupe warfarine (RRI : 2,3; IC à 95 % : 0,6-8,9; p = 0,25).
Conclusions
L’HBPM et la warfarine semblent aussi efficaces l’une que l’autre pour ce qui est
de prévenir la thrombose dans les cas de gros anévrismes coronariens après une maladie
de Kawasaki, bien que les événements associés à la thromboprophylaxie secondaire et
les problèmes liés à l’innocuité aient été peu nombreux. Les résultats semblent indiquer
que tous les patients présentant de gros anévrismes coronariens de score Z ≥ 10 devraient
recevoir une anticoagulothérapie, mais le choix de l’agent thérapeutique devrait aussi
tenir compte des facteurs de risque secondaires et des préférences du patient.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Canadian Journal of CardiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Epidemiology of Kawasaki disease in Asia, Europe, and the United States.J Epidemiol. 2012; 22: 79-85
- Epidemiology of Kawasaki disease in Canada 2004 to 2014: comparison of surveillance using administrative data vs periodic medical record review.Can J Cardiol. 2018; 34: 303-309
- Size of coronary aneurysm as a determinant factor of the prognosis in Kawasaki disease: clinicopathologic study of coronary aneurysms.Prog Clin Biol Res. 1987; 250: 519-520
- Long-term prognosis of giant coronary aneurysm in Kawasaki disease: an angiographic study.J Pediatr. 1987; 111: 705-710
- Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association.Circulation. 2017; 135: e927-e999
- Anticoagulation in the acute and long-term management of Kawasaki disease.Prog Pediatr Cardiol. 2004; 19: 179-188
- Structure and mechanism of activation of vitamin K antagonists.in: Poller L. Hirsh J. Oral Anticoagulants. Arnold/Hodder Headline Group and Oxford Press, London1996: 9-29
- A multicenter, randomized trial comparing heparin/warfarin and acetylsalicylic acid as primary thromboprophylaxis for 2 years after the Fontan procedure in children.J Am Coll Cardiol. 2011; 58: 645-651
- Safety and efficacy of warfarin therapy in Kawasaki disease.J Pediatr. 2017; 189: 61-65
- The use of low molecular weight heparin in pediatric patients: a prospective cohort study.J Pediatr. 2000; 136: 439-445
- Development and preliminary evaluation of the KIDCLOT PAC QL: a new health-related quality of life measure for pediatric long-term anticoagulation therapy.Thromb Res. 2010; 126: e116-e121
- Effects of long-term low-molecular-weight heparin on fractures and bone density in non-pregnant adults: a systematic review with meta-analysis.J Gen Intern Med. 2016; 31: 947-957
- Difference between persistent aneurysm, regressed aneurysm, and coronary dilation in Kawasaki disease: an optical coherence tomography study.Can J Cardiol. 2018; 34: 1120-1128
- Long-term anticoagulation in Kawasaki disease: Initial use of low molecular weight heparin is a viable option for patients with severe coronary artery abnormalities.Pediatr Cardiol. 2010; 31: 834-842
- International Kawasaki Disease Registry. Medium-term complications associated with coronary artery aneurysms after Kawasaki Disease: a study from the International Kawasaki Disease Registry.J Am Heart Assoc. 2020; 9: e016440
- Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support.J Biomed Inform. 2009; 42: 377-381
- Coronary artery involvement in children with Kawasaki disease: risk factors from analysis of serial normalized measurements.Circulation. 2007; 116: 174-179
- Warfarin therapy for giant aneurysm prevents myocardial infarction in Kawasaki disease.Pediatr Cardiol. 2008; 29: 398-401
- Multicenter and retrospective case study of warfarin and aspirin combination therapy in patients with giant coronary aneurysms caused by Kawasaki disease.Circ J. 2009; 73: 1319-1323
- Safety and efficacy of warfarin plus aspirin combination therapy for giant coronary artery aneurysm secondary to Kawasaki disease: a meta-analysis.Cardiology. 2014; 129: 55-64
- Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding.Can Med Assoc J. 2007; 177: 347-351
- Gastrointestinal ulcers, role of aspirin, and clinical outcomes: pathobiology, diagnosis, and treatment.J Multidiscip Healthc. 2014; 7: 137-146
- Warfarin drug interactions. StatPearls 2019.(Available at:)
- Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines.Chest. 2012; 141: e44S-88S
- Kawasaki disease with coronary artery aneurysms: psychosocial impact on parents and children.J Pediatr Health Care. 2017; 31: 459-469
- Different contributions of polymorphisms in VKORC1 and CYP2C9 to intra- and inter-population differences in maintenance dose of warfarin in Japanese, Caucasians and African-Americans.Pharmacogenet Genomics. 2006; 16: 101-110
- Protamine reversal of low molecular weight heparin: clinically effective?.Blood Coagul Fibrinolysis. 2011; 22: 565-570
- Novel oral anticoagulants for atrial fibrillation.Singapore Med J. 2015; 56: 657-658
- New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events.Ther Clin Risk Manag. 2015; 11: 967-977
Article info
Publication history
Published online: January 29, 2020
Accepted:
January 16,
2020
Received:
December 3,
2019
Footnotes
See editorial by Butt, pages 1566—1568 of this issue.
See page 1606 for disclosure information.
Identification
Copyright
© 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Kawasaki Disease: Complex Long-term Issues for Pediatric and Adult CardiologistsCanadian Journal of CardiologyVol. 36Issue 10
- PreviewKawasaki disease (KD) is a systemic inflammatory vasculitis1 that affects medium-sized vessels and is characterized by a complex response with elevated plasma cytokines. Although the etiology of KD remains uncertain, epidemiological studies suggest a probable role of infection in a patient with a genetic predisposition. Most children respond to intravenous immunoglobulin (IVIG) and aspirin,1 but there are data showing KD that is resistant to initial IVIG therapy, in which both inflammatory (TNF-α, IL-6, IL-8, IL-17, IFN-γ, G-CSF, MCP-1 and sIL-2Rα) and anti-inflammatory (IL-10, sTNFR1, and sTNFR2) cytokine levels are simultaneously elevated.
- Full-Text
- Preview
