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

doi:10.1016/j.cjca.2020.01.016

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

Medicine

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

18 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	1598-1607
Número de páginas	10
Publicación	Canadian Journal of Cardiology
Volumen	36
N.º	10
DOI	https://doi.org/10.1016/j.cjca.2020.01.016
Estado	Published - oct. 2020

Nota bibliográfica

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, Montréal), 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

ASJC Scopus Subject Areas

Cardiology and Cardiovascular Medicine

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10.1016/j.cjca.2020.01.016

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@article{7d45433859dc44c3b34972d68d88914a,

title = "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.",

author = "{International Kawasaki Disease Registry} and Cedric Manlhiot and Newburger, {Jane W.} and Tisiana Low and Nagib Dahdah and Mackie, {Andrew S.} and Geetha Raghuveer and Giglia, {Therese M.} and Frederic Dallaire and Mathew Mathew and Kyle Runeckles and Elfriede Pahl and Harahsheh, {Ashraf S.} and Kambiz Norozi and {de Ferranti}, {Sarah D.} and Kevin Friedman and Yetman, {Anji T.} and Shelby Kutty and Tapas Mondal and McCrindle, {Brian W.} and Altman, {Carolyn A.} and Anderson, {Brett R.} and Elizabeth Braunlin and Burns, {Jane C.} and Carr, {Michael R.} and Choueiter, {Nadine F.} and Colyer, {Jessica H.} and Andrew Crean and Adam Dempsey and Laurent Desjardins and Rejane Dillenburg and Audrey Dionne and Anna Ferris and Michael Gewitz and Grcic, {Michelle M.} and Greenway, {Steven C.} and Elodie Hamel-Perrault and Harris, {Kevin C.} and Christina Hayden-Rush and Hill, {Kevin D.} and Supriya Jain and Jone, {Pei Ni} and Kimball, {Thomas R.} and Lang, {Sean M.} and Li, {Jennifer S.} and Lin, {Ming Tai} and Mahle, {William T.} and McHugh, {Kimberly E.} and Portman, {Michael A.} and Claudia Renaud and Andrew Warren",

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{\'e}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{\textquoteright}s Health Foundation of London , Ontario (Kambiz Norozi). Publisher Copyright: {\textcopyright} 2020 Canadian Cardiovascular Society",

year = "2020",

month = oct,

doi = "10.1016/j.cjca.2020.01.016",

language = "English",

volume = "36",

pages = "1598--1607",

journal = "Canadian Journal of Cardiology",

issn = "0828-282X",

publisher = "Pulsus Group Inc.",

number = "10",

}

TY - JOUR

T1 - Low-Molecular-Weight Heparin vs Warfarin for Thromboprophylaxis in Children With Coronary Artery Aneurysms After Kawasaki Disease

T2 - A Pragmatic Registry Trial

AU - International Kawasaki Disease Registry

AU - Manlhiot, Cedric

AU - Newburger, Jane W.

AU - Low, Tisiana

AU - Dahdah, Nagib

AU - Mackie, Andrew S.

AU - Raghuveer, Geetha

AU - Giglia, Therese M.

AU - Dallaire, Frederic

AU - Mathew, Mathew

AU - Runeckles, Kyle

AU - Pahl, Elfriede

AU - Harahsheh, Ashraf S.

AU - Norozi, Kambiz

AU - de Ferranti, Sarah D.

AU - Friedman, Kevin

AU - Yetman, Anji T.

AU - Kutty, Shelby

AU - Mondal, Tapas

AU - McCrindle, Brian W.

AU - Altman, Carolyn A.

AU - Anderson, Brett R.

AU - Braunlin, Elizabeth

AU - Burns, Jane C.

AU - Carr, Michael R.

AU - Choueiter, Nadine F.

AU - Colyer, Jessica H.

AU - Crean, Andrew

AU - Dempsey, Adam

AU - Desjardins, Laurent

AU - Dillenburg, Rejane

AU - Dionne, Audrey

AU - Ferris, Anna

AU - Gewitz, Michael

AU - Grcic, Michelle M.

AU - Greenway, Steven C.

AU - Hamel-Perrault, Elodie

AU - Harris, Kevin C.

AU - Hayden-Rush, Christina

AU - Hill, Kevin D.

AU - Jain, Supriya

AU - Jone, Pei Ni

AU - Kimball, Thomas R.

AU - Lang, Sean M.

AU - Li, Jennifer S.

AU - Lin, Ming Tai

AU - Mahle, William T.

AU - McHugh, Kimberly E.

AU - Portman, Michael A.

AU - Renaud, Claudia

AU - Warren, Andrew

N1 - 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, Montréal), 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

PY - 2020/10

Y1 - 2020/10

N2 - 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.

AB - 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.

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

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