Dabigatran for Treatment and Secondary Prevention of Venous Thromboembolism in Pediatric Congenital Heart Disease
Background Congenital heart disease (CHD) is common in children and associated with greater risk of thrombotic complications. Management of these complications with standard‐of‐care treatment is suboptimal for these children. Methods and Results The effectiveness and safety of dabigatran were demons...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.122.028957 |
| _version_ | 1826988170199171072 |
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| author | Manuela Albisetti Igor Tartakovsky Jacqueline Halton Lisa Bomgaars Elizabeth Chalmers Lesley G. Mitchell Matteo Luciani Ildar Nurmeev Kirill Gorbatikov Corinna Miede Martina Brueckmann Leonardo R. Brandão |
| author_facet | Manuela Albisetti Igor Tartakovsky Jacqueline Halton Lisa Bomgaars Elizabeth Chalmers Lesley G. Mitchell Matteo Luciani Ildar Nurmeev Kirill Gorbatikov Corinna Miede Martina Brueckmann Leonardo R. Brandão |
| author_sort | Manuela Albisetti |
| collection | DOAJ |
| description | Background Congenital heart disease (CHD) is common in children and associated with greater risk of thrombotic complications. Management of these complications with standard‐of‐care treatment is suboptimal for these children. Methods and Results The effectiveness and safety of dabigatran were demonstrated in pivotal pediatric studies for the treatment of acute venous thromboembolism (VTE; NCT01895777) and secondary VTE prevention (NCT02197416). We report safety and efficacy outcomes from subgroup analyses of these studies for children with CHD (diagnosed according to local practice) and those without. In NCT01895777, 17/21 (81.0%) and 16/27 (59.3%) patients with CHD (including cyanotic) treated with dabigatran and standard of care, respectively, met the primary end point (complete thrombus resolution, freedom from recurrent VTE, and freedom from VTE‐related death; odds ratio [OR], 0.34 [95% CI, 0.08–1.23]). In patients without CHD, 41.0% (n=64) versus 34.9% (n=22) achieved this end point with the respective treatments (OR, 0.77 [95% CI, 0.42–1.41]). Although numerical differences were observed, no heterogeneity in treatment effect of dabigatran on the composite primary end point was detected in patients with and without CHD (interaction P =0.2674). In NCT02197416, recurrent VTE at 12 months occurred in 0/17 patients with CHD versus 3/194 (1.5%) without. No patient with CHD experienced major or clinically relevant nonmajor bleeding events. Conclusions Data on favorable anticoagulant alternatives for the unmet needs of children with CHD are emerging, and our exploratory results suggest that dabigatran could be an appropriate treatment choice, although challenging sample size limitations in pediatric studies require cautious interpretation of findings. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01895777, NCT02197416. |
| first_indexed | 2024-03-07T23:32:56Z |
| format | Article |
| id | doaj.art-b638d23a24724bb0bb3666d450e82e48 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2025-02-18T07:48:33Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-b638d23a24724bb0bb3666d450e82e482024-11-05T14:15:40ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-02-0113410.1161/JAHA.122.028957Dabigatran for Treatment and Secondary Prevention of Venous Thromboembolism in Pediatric Congenital Heart DiseaseManuela Albisetti0Igor Tartakovsky1Jacqueline Halton2Lisa Bomgaars3Elizabeth Chalmers4Lesley G. Mitchell5Matteo Luciani6Ildar Nurmeev7Kirill Gorbatikov8Corinna Miede9Martina Brueckmann10Leonardo R. Brandão11Hematology Department University Children’s Hospital Zürich SwitzerlandBoehringer Ingelheim International GmbH Ingelheim GermanyChildren’s Hospital of Eastern Ontario University of Ottawa Ottawa Ontario CanadaDepartment of Pediatrics Texas Children’s Hospital, Baylor College of Medicine Houston TX USARoyal Hospital for Children Glasgow Scotland UKUniversity of Alberta Edmonton Alberta CanadaPediatric Hematology/Oncology Department Pediatric Hospital Bambino Gesù Rome ItalyPediatric Hospital, Republic of Tatarstan Kazan Medical University Kazan Russian FederationPediatric Cardiovascular Surgery Regional Hospital #1 Tyumen Region Russian Federationmainanalytics GmbH Sulzbach (Taunus) GermanyBoehringer Ingelheim International GmbH Ingelheim GermanyThe Hospital for Sick Children University of Toronto Toronto Ontario CanadaBackground Congenital heart disease (CHD) is common in children and associated with greater risk of thrombotic complications. Management of these complications with standard‐of‐care treatment is suboptimal for these children. Methods and Results The effectiveness and safety of dabigatran were demonstrated in pivotal pediatric studies for the treatment of acute venous thromboembolism (VTE; NCT01895777) and secondary VTE prevention (NCT02197416). We report safety and efficacy outcomes from subgroup analyses of these studies for children with CHD (diagnosed according to local practice) and those without. In NCT01895777, 17/21 (81.0%) and 16/27 (59.3%) patients with CHD (including cyanotic) treated with dabigatran and standard of care, respectively, met the primary end point (complete thrombus resolution, freedom from recurrent VTE, and freedom from VTE‐related death; odds ratio [OR], 0.34 [95% CI, 0.08–1.23]). In patients without CHD, 41.0% (n=64) versus 34.9% (n=22) achieved this end point with the respective treatments (OR, 0.77 [95% CI, 0.42–1.41]). Although numerical differences were observed, no heterogeneity in treatment effect of dabigatran on the composite primary end point was detected in patients with and without CHD (interaction P =0.2674). In NCT02197416, recurrent VTE at 12 months occurred in 0/17 patients with CHD versus 3/194 (1.5%) without. No patient with CHD experienced major or clinically relevant nonmajor bleeding events. Conclusions Data on favorable anticoagulant alternatives for the unmet needs of children with CHD are emerging, and our exploratory results suggest that dabigatran could be an appropriate treatment choice, although challenging sample size limitations in pediatric studies require cautious interpretation of findings. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01895777, NCT02197416.https://www.ahajournals.org/doi/10.1161/JAHA.122.028957childrencongenital heart diseasedabigatranvenous thromboembolism |
| spellingShingle | Manuela Albisetti Igor Tartakovsky Jacqueline Halton Lisa Bomgaars Elizabeth Chalmers Lesley G. Mitchell Matteo Luciani Ildar Nurmeev Kirill Gorbatikov Corinna Miede Martina Brueckmann Leonardo R. Brandão Dabigatran for Treatment and Secondary Prevention of Venous Thromboembolism in Pediatric Congenital Heart Disease Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease children congenital heart disease dabigatran venous thromboembolism |
| title | Dabigatran for Treatment and Secondary Prevention of Venous Thromboembolism in Pediatric Congenital Heart Disease |
| title_full | Dabigatran for Treatment and Secondary Prevention of Venous Thromboembolism in Pediatric Congenital Heart Disease |
| title_fullStr | Dabigatran for Treatment and Secondary Prevention of Venous Thromboembolism in Pediatric Congenital Heart Disease |
| title_full_unstemmed | Dabigatran for Treatment and Secondary Prevention of Venous Thromboembolism in Pediatric Congenital Heart Disease |
| title_short | Dabigatran for Treatment and Secondary Prevention of Venous Thromboembolism in Pediatric Congenital Heart Disease |
| title_sort | dabigatran for treatment and secondary prevention of venous thromboembolism in pediatric congenital heart disease |
| topic | children congenital heart disease dabigatran venous thromboembolism |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.122.028957 |
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