Cedric Manlhiot1, Jane W Newburger2, Tisiana Low1, Nagib Dahdah3, Andrew S Mackie4, Geetha Raghuveer5, Therese M Giglia6, Frederic Dallaire7, Mathew Mathew1, Kyle Runeckles1, Elfriede Pahl8, Ashraf S Harahsheh9, Kambiz Norozi10, Sarah D de Ferranti2, Kevin Friedman2, Anji T Yetman11, Shelby Kutty11, Tapas Mondal12, Brian W McCrindle13. 1. Division of Cardiology, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada. 2. Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 3. Division of Pediatric Cardiology, Centre Hospitalier Universitaire Ste-Justine, University of Montréal, Montréal, Québec, Canada. 4. Stollery Children's Hospital, Edmonton, Alberta, Canada. 5. Children's Mercy Hospital, Kansas City, Missouri, USA. 6. Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. 7. Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec, Canada. 8. Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA. 9. Pediatrics-Cardiology, Children's National Health System/George Washington University, Washington, District of Columbia, USA. 10. Department of Paediatrics, Western University, London, Ontario, Canada. 11. Children's Hospital and Medical Center of Omaha, Omaha, Nebraska, USA. 12. McMaster Children's Hospital, Hamilton, Ontario, Canada. 13. Division of Cardiology, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada. Electronic address: brian.mccrindle@sickkids.ca.
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.
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: Matthew D Elias; Brian W McCrindle; Guillermo Larios; Nadine F Choueiter; Nagib Dahdah; Ashraf S Harahsheh; Supriya Jain; Cedric Manlhiot; Michael A Portman; Geetha Raghuveer; Therese M Giglia; Audrey Dionne Journal: CJC Open Date: 2020-09-11