Yan Xu1, Sam Schulman2, Dar Dowlatshahi3, Anne M Holbrook4, Christopher S Simpson5, Lois E Shepherd6, Philip S Wells3, Antonio Giulivi7, Tara Gomes8, Muhammad Mamdani9, Wayne Khuu10, Eliot Frymire11, Ana P Johnson12. 1. Department of Medicine, University of Toronto, Toronto, ON, Canada. 2. Department of Medicine, McMaster University, Hamilton, ON, Canada. 3. Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada. 4. Department of Medicine, McMaster University, Hamilton, ON, Canada; Division of Clinical Pharmacology and Toxicology, McMaster University, Hamilton, ON, Canada. 5. Department of Medicine, Queen's University, Kingston, ON, Canada. 6. Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada. 7. Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, ON, Canada. 8. Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada; Institute for Clinical Evaluative Sciences, St. Michael's Hospital, Toronto, ON, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada. 9. Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada; Institute for Clinical Evaluative Sciences, St. Michael's Hospital, Toronto, ON, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada. 10. Institute for Clinical Evaluative Sciences, St. Michael's Hospital, Toronto, ON, Canada. 11. Centre for Health Services and Policy Research, Queen's University, Kingston, ON, Canada. 12. Centre for Health Services and Policy Research, Queen's University, Kingston, ON, Canada; Department of Public Health Sciences, Queen's University, Kingston, ON, Canada. Electronic address: ana.johnson@queensu.ca.
Abstract
BACKGROUND: Direct oral anticoagulants (DOACs) have expanded the armamentarium for antithrombotic therapy. Although DOAC-related major bleeding was associated with favorable outcomes compared with warfarin in clinical trials, warfarin effects were reversed in < 40% of cases, raising concerns about the generalizability of this finding. METHODS: Consecutive patients ≥ 66 years presented to five tertiary care hospitals across three cities in Ontario, Canada from October 2010 to March 2015 with diagnoses that included hemorrhage. Charts were screened for association with DOAC or warfarin use; eligible cases were abstracted and linked to administrative databases. RESULTS: Among 19,061 records screened, 2,002 (460 receiving DOAC, 1,542 receiving warfarin) were eligible. Reversal agents (72.9% vitamin K, 40.7% prothrombin complex concentrates) were frequently used in warfarin bleeding events. Red blood cell transfusions occurred more often in DOAC bleeding events than in warfarin events (52.0% vs 39.5%; adjusted relative risk [aRR], 1.32; 95% CI, 1.19-2.47). However, units of blood products transfused were not different between the two groups. Thirty-four DOAC cases (7.4%) received activated prothrombin complex concentrates or recombinant factor VIIa. In-hospital mortality was lower following DOAC bleeding events (9.8% vs 15.2%; aRR, 0.66; 95% CI, 0.49-0.89), although differences in 30-day mortality did not reach statistical significance (12.6% vs 16.3%; aRR, 0.79; 95% CI, 0.61-1.03). CONCLUSIONS: In this unselected cohort of patients with oral anticoagulant-related hemorrhage with high rates of warfarin reversal, in-hospital mortality was lower among DOAC-associated bleeding events. These findings support the safety of DOACs in routine care and present useful baseline measures for evaluations of DOAC-specific reversal agents.
BACKGROUND: Direct oral anticoagulants (DOACs) have expanded the armamentarium for antithrombotic therapy. Although DOAC-related major bleeding was associated with favorable outcomes compared with warfarin in clinical trials, warfarin effects were reversed in < 40% of cases, raising concerns about the generalizability of this finding. METHODS: Consecutive patients ≥ 66 years presented to five tertiary care hospitals across three cities in Ontario, Canada from October 2010 to March 2015 with diagnoses that included hemorrhage. Charts were screened for association with DOAC or warfarin use; eligible cases were abstracted and linked to administrative databases. RESULTS: Among 19,061 records screened, 2,002 (460 receiving DOAC, 1,542 receiving warfarin) were eligible. Reversal agents (72.9% vitamin K, 40.7% prothrombin complex concentrates) were frequently used in warfarinbleeding events. Red blood cell transfusions occurred more often in DOACbleeding events than in warfarin events (52.0% vs 39.5%; adjusted relative risk [aRR], 1.32; 95% CI, 1.19-2.47). However, units of blood products transfused were not different between the two groups. Thirty-four DOAC cases (7.4%) received activated prothrombin complex concentrates or recombinant factor VIIa. In-hospital mortality was lower following DOACbleeding events (9.8% vs 15.2%; aRR, 0.66; 95% CI, 0.49-0.89), although differences in 30-day mortality did not reach statistical significance (12.6% vs 16.3%; aRR, 0.79; 95% CI, 0.61-1.03). CONCLUSIONS: In this unselected cohort of patients with oral anticoagulant-related hemorrhage with high rates of warfarin reversal, in-hospital mortality was lower among DOAC-associated bleeding events. These findings support the safety of DOACs in routine care and present useful baseline measures for evaluations of DOAC-specific reversal agents.
Authors: Edelgard Lindhoff-Last; Eva Herrmann; Simone Lindau; Stavros Konstantinides; Oliver Grottke; Ulrike Nowak-Goettl; Jessica Lucks; Barbara Zydek; Christian von Heymann; Ingvild Birschmann; Ariane Sümnig; Jan Beyer-Westendorf; Sebastian Schellong; Patrick Meybohm; Andreas Greinacher Journal: Dtsch Arztebl Int Date: 2020-05-01 Impact factor: 5.594
Authors: Walter Bialkowski; Sylvia Tan; Alan E Mast; Joseph E Kiss; Daryl Kor; Jerome Gottschall; Yanyun Wu; Nareg Roubinian; Darrell Triulzi; Steve Kleinman; Young Choi; Donald Brambilla; Ann Zimrin Journal: Thromb Res Date: 2019-11-25 Impact factor: 3.944