Jürgen H Prochaska1,2,3,4, Sebastian Göbel5,6, Markus Nagler7,8, Torben Knöpfler7,9, Lisa Eggebrecht7,9, Heidrun Lamparter7,8, Marina Panova-Noeva8,5,9, Karsten Keller8,6, Meike Coldewey8, Christoph Bickel10, Michael Lauterbach11, Roland Hardt12, Christine Espinola-Klein9,6, Hugo Ten Cate8,13, Thomas Rostock14, Thomas Münzel8,5,9,6, Philipp S Wild15,16,17,18. 1. Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany. juergen.prochaska@unimedizin-mainz.de. 2. Center for Thrombosis and Hemostasis, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Mainz, Germany. juergen.prochaska@unimedizin-mainz.de. 3. German Center for Cardiovascular Research (DZHK), Partner Site RhineMain, Mainz, Germany. juergen.prochaska@unimedizin-mainz.de. 4. Center for Translational Vascular Biology (CTVB), University Medical Center Mainz, Johannes Gutenberg-University Mainz, Mainz, Germany. juergen.prochaska@unimedizin-mainz.de. 5. German Center for Cardiovascular Research (DZHK), Partner Site RhineMain, Mainz, Germany. 6. Center for Cardiology, Cardiology I, University Medical Center Mainz, Johannes Gutenberg University-Mainz, Mainz, Germany. 7. Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany. 8. Center for Thrombosis and Hemostasis, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Mainz, Germany. 9. Center for Translational Vascular Biology (CTVB), University Medical Center Mainz, Johannes Gutenberg-University Mainz, Mainz, Germany. 10. Department of Medicine I, Federal Armed Forces Central Hospital, Koblenz, Germany. 11. Department of Medicine 3, Barmherzige Brüder Hospital, Trier, Germany. 12. Center for General Medicine and Geriatric Medicine, University Medical Center Mainz, Johannes Gutenberg University-Mainz, Mainz, Germany. 13. Thrombosis Expertise Center Maastricht, Cardiovascular Research Institute Maastricht and Maastricht University Medical Center, 6200, Maastricht, The Netherlands. 14. Center for Cardiology, Cardiology II, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Mainz, Germany. 15. Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany. philipp.wild@unimedizin-mainz.de. 16. Center for Thrombosis and Hemostasis, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Mainz, Germany. philipp.wild@unimedizin-mainz.de. 17. German Center for Cardiovascular Research (DZHK), Partner Site RhineMain, Mainz, Germany. philipp.wild@unimedizin-mainz.de. 18. Center for Translational Vascular Biology (CTVB), University Medical Center Mainz, Johannes Gutenberg-University Mainz, Mainz, Germany. philipp.wild@unimedizin-mainz.de.
Abstract
BACKGROUND: Oral anticoagulation therapy in individuals with atrial fibrillation (AF) reduces the risk of thromboembolic events at cost of an increased bleeding risk. Whether anticoagulation-related outcomes differ between patients with paroxysmal and sustained AF receiving anticoagulation is controversially discussed. METHODS: In the present analysis of the prospective multi-center cohort study thrombEVAL, the incidence of anticoagulation-related adverse events was analyzed according to the AF phenotype. Information on outcome was centrally recorded over 3 years, validated via medical records and adjudicated by an independent review panel. Study monitoring was provided by an independent institution. RESULTS: Overall, the sample comprised 1089 AF individuals, of whom n = 398 had paroxysmal AF and n = 691 experienced sustained AF. In Cox regression analysis with adjustment for potential confounders, sustained AF indicated an independently elevated risk of clinically relevant bleeding compared to paroxysmal AF [hazard ratio (HR) 1.40 (1.02; 1.93); P = 0.038]. For clinically relevant bleeding, a significant interaction of the pattern of AF type with concomitant heart failure (HF) was detected: HRHF 2.45 (1.51, 3.98) vs. HRno HF 0.85 (0.55, 1.34); Pinteraction = 0.003. In HF patients, sustained AF indicated also an elevated risk of major bleeding [HR 2.25 (1.26, 4.20); P = 0.006]. A simplified HAS-BLED score incorporating only information on age (> 65 years), bleeding history, and HF with sustained AF demonstrated better discriminative performance for clinically relevant bleeding than the original version: AUCHAS-BLED: 0.583 vs. AUCsimplifiedHAS-BLED: 0.642 (P = 0.004). CONCLUSIONS: In HF patients receiving oral anticoagulation, sustained AF indicates a substantially elevated risk of bleeding. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov , identifier: NCT01809015.
BACKGROUND: Oral anticoagulation therapy in individuals with atrial fibrillation (AF) reduces the risk of thromboembolic events at cost of an increased bleeding risk. Whether anticoagulation-related outcomes differ between patients with paroxysmal and sustained AF receiving anticoagulation is controversially discussed. METHODS: In the present analysis of the prospective multi-center cohort study thrombEVAL, the incidence of anticoagulation-related adverse events was analyzed according to the AF phenotype. Information on outcome was centrally recorded over 3 years, validated via medical records and adjudicated by an independent review panel. Study monitoring was provided by an independent institution. RESULTS: Overall, the sample comprised 1089 AF individuals, of whom n = 398 had paroxysmal AF and n = 691 experienced sustained AF. In Cox regression analysis with adjustment for potential confounders, sustained AF indicated an independently elevated risk of clinically relevant bleeding compared to paroxysmal AF [hazard ratio (HR) 1.40 (1.02; 1.93); P = 0.038]. For clinically relevant bleeding, a significant interaction of the pattern of AF type with concomitant heart failure (HF) was detected: HRHF 2.45 (1.51, 3.98) vs. HRno HF 0.85 (0.55, 1.34); Pinteraction = 0.003. In HF patients, sustained AF indicated also an elevated risk of major bleeding [HR 2.25 (1.26, 4.20); P = 0.006]. A simplified HAS-BLED score incorporating only information on age (> 65 years), bleeding history, and HF with sustained AF demonstrated better discriminative performance for clinically relevant bleeding than the original version: AUCHAS-BLED: 0.583 vs. AUCsimplifiedHAS-BLED: 0.642 (P = 0.004). CONCLUSIONS: In HF patients receiving oral anticoagulation, sustained AF indicates a substantially elevated risk of bleeding. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov , identifier: NCT01809015.
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