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Canadian Journal of Cardiology

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

Published:January 29, 2020DOI:https://doi.org/10.1016/j.cjca.2020.01.016

      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.
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      Linked Article

      • Kawasaki Disease: Complex Long-term Issues for Pediatric and Adult Cardiologists
        Canadian Journal of CardiologyVol. 36Issue 10
        • Preview
          Kawasaki 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.
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