Skip to main content
Top
Published in: BMC Cardiovascular Disorders 1/2016

Open Access 01-12-2016 | Research article

Thromboembolic events, bleeding, and drug discontinuation in patients with atrial fibrillation on anticoagulation: a prospective hospital-based registry

Authors: Oliver Königsbrügge, Alexander Simon, Hans Domanovits, Ingrid Pabinger, Cihan Ay

Published in: BMC Cardiovascular Disorders | Issue 1/2016

Login to get access

Abstract

Background

The clinical practice of stroke prevention in atrial fibrillation (AF) with direct oral anticoagulants (DOACS) differs from anticoagulation in randomized trial patients. We investigated the risk of thromboembolism, bleeding, and drug discontinuation in a hospital-based real-world setting.

Methods

All-comer patients with non-valvular AF were recruited into a registry at an academic tertiary care center. After informed consent, patients underwent a personal structured interview including medical history, past and current anticoagulation, and returned for follow-up after 6–12 months.

Results

The registry comprised 282 patients (42% women, median age 71 years) with a median CHA2DS2-Vasc-Score of 4 (25. to 75. percentile 2.5–5), who were prospectively followed 285 days in median. At inclusion, 118 patients took vitamin-K-antagonists, 33 dabigatran, 87 rivaroxaban, 30 apixaban, 5 low-molecular-weight heparin, and 9 were on no anticoagulant. Occurrence of stroke (rate 2.8/100 patient-years), was associated with prior stroke (hazard ratio [HR] 18.5, 95% confidence interval 2.16–159), increased HbA1c (HR per 1% increase 1.71, 1.20–2.45) and borderline significantly associated with vascular disease (HR 8.33, 0.97–71.3). Further we observed a high rate of major bleeding (2.8/100 patient-years), clinically relevant non-major bleeding (4.1/100 patient-years), and venous thromboembolism (2.8/100 patient-years). Anticoagulation was discontinued by 80 patients (36.9/100 patient-years), and diabetes (HR 2.31, 1.32–4.02), history of bleeding (HR 2.51, 1.44–4.37) and elevated leucocyte count (HR per 1G/l increase 1.02, 1.00–1.05) were associated with increased risk of discontinuation.

Conclusions

In this hospital-based registry, patients with atrial fibrillation had an increased risk of thromboembolic events despite anticoagulation. The low drug persistence may be attributable to distinct comorbid conditions and bleeding complications.
Literature
1.
go back to reference Hart RG, Palacio S, Pearce LA. Atrial Fibrillation, Stroke, and Acute Antithrombotic Therapy: Analysis of Randomized Clinical Trials. Stroke. 2002;33:2722–7.CrossRefPubMed Hart RG, Palacio S, Pearce LA. Atrial Fibrillation, Stroke, and Acute Antithrombotic Therapy: Analysis of Randomized Clinical Trials. Stroke. 2002;33:2722–7.CrossRefPubMed
2.
go back to reference Beyer-Westendorf J, Ebertz F, Förster K, Gelbricht V, Michalski F, Köhler C, et al. Effectiveness and safety of dabigatran therapy in daily-care patients with atrial fibrillation Results from the Dresden NOAC Registry. Thromb Haemost. 2015;113:1247–57.CrossRefPubMed Beyer-Westendorf J, Ebertz F, Förster K, Gelbricht V, Michalski F, Köhler C, et al. Effectiveness and safety of dabigatran therapy in daily-care patients with atrial fibrillation Results from the Dresden NOAC Registry. Thromb Haemost. 2015;113:1247–57.CrossRefPubMed
3.
go back to reference O’Brien EC, Kim S, Thomas L, Fonarow GC, Kowey PR, Mahaffey KW, et al. Clinical Characteristics, Oral Anticoagulation Patterns, and Outcomes of Medicaid Patients With Atrial Fibrillation: Insights From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF I) Registry. J Am Heart Assoc. 2016;5:e002721.CrossRefPubMedPubMedCentral O’Brien EC, Kim S, Thomas L, Fonarow GC, Kowey PR, Mahaffey KW, et al. Clinical Characteristics, Oral Anticoagulation Patterns, and Outcomes of Medicaid Patients With Atrial Fibrillation: Insights From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF I) Registry. J Am Heart Assoc. 2016;5:e002721.CrossRefPubMedPubMedCentral
4.
go back to reference Yao X, Abraham NS, Alexander GC, Crown W, Montori VM, Sangaralingham LR, et al. Effect of Adherence to Oral Anticoagulants on Risk of Stroke and Major Bleeding Among Patients With Atrial Fibrillation. J Am Heart Assoc. 2016;5:1–12. Yao X, Abraham NS, Alexander GC, Crown W, Montori VM, Sangaralingham LR, et al. Effect of Adherence to Oral Anticoagulants on Risk of Stroke and Major Bleeding Among Patients With Atrial Fibrillation. J Am Heart Assoc. 2016;5:1–12.
5.
go back to reference Palomäki A, Mustonen P, Hartikainen JEK, Nuotio I, Kiviniemi T, Ylitalo A, et al. Underuse of anticoagulation in stroke patients with atrial fibrillation - the FibStroke Study. Eur J Neurol. 2016;23:133–9.CrossRefPubMed Palomäki A, Mustonen P, Hartikainen JEK, Nuotio I, Kiviniemi T, Ylitalo A, et al. Underuse of anticoagulation in stroke patients with atrial fibrillation - the FibStroke Study. Eur J Neurol. 2016;23:133–9.CrossRefPubMed
6.
go back to reference Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.CrossRefPubMed Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.CrossRefPubMed
7.
go back to reference Patel M, Mahaffey K, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.CrossRefPubMed Patel M, Mahaffey K, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.CrossRefPubMed
8.
go back to reference Granger CB, Alexander JH, McMurray JJV, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92.CrossRefPubMed Granger CB, Alexander JH, McMurray JJV, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92.CrossRefPubMed
9.
go back to reference Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369:2093–104.CrossRefPubMed Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369:2093–104.CrossRefPubMed
10.
go back to reference Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3:692–4.CrossRefPubMed Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3:692–4.CrossRefPubMed
11.
go back to reference Kaatz S, Ahmad D, Spyropoulos AC, Schulman S. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: Communication from the SSC of the ISTH. J Thromb Haemost. 2015;13:2119–26.CrossRefPubMed Kaatz S, Ahmad D, Spyropoulos AC, Schulman S. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: Communication from the SSC of the ISTH. J Thromb Haemost. 2015;13:2119–26.CrossRefPubMed
12.
go back to reference Cramer JA, Roy A, Burrell A, Fairchild CJ, Fuldeore MJ, Ollendorf DA, et al. Medication compliance and persistence: Terminology and definitions. Value Heal. 2008;11:44–7.CrossRef Cramer JA, Roy A, Burrell A, Fairchild CJ, Fuldeore MJ, Ollendorf DA, et al. Medication compliance and persistence: Terminology and definitions. Value Heal. 2008;11:44–7.CrossRef
13.
go back to reference Graham DJ, Reichman ME, Wernecke M, Zhang R, Southworth MR, Levenson M, et al. Cardiovascular, Bleeding, and Mortality Risks in Elderly Medicare Patients Treated With Dabigatran or Warfarin for Nonvalvular Atrial Fibrillation. Circulation. 2015;131:157–64.CrossRefPubMed Graham DJ, Reichman ME, Wernecke M, Zhang R, Southworth MR, Levenson M, et al. Cardiovascular, Bleeding, and Mortality Risks in Elderly Medicare Patients Treated With Dabigatran or Warfarin for Nonvalvular Atrial Fibrillation. Circulation. 2015;131:157–64.CrossRefPubMed
14.
go back to reference Korenstra J, Wijtvliet EPJ, Veeger NJGM, Geluk CA, Bartels GL, Posma JL, et al. Effectiveness and safety of dabigatran versus acenocoumarol in “real-world” patients with atrial fibrillation. Europace. 2016;18:1319–27. Korenstra J, Wijtvliet EPJ, Veeger NJGM, Geluk CA, Bartels GL, Posma JL, et al. Effectiveness and safety of dabigatran versus acenocoumarol in “real-world” patients with atrial fibrillation. Europace. 2016;18:1319–27.
15.
go back to reference Hecker J, Marten S, Keller L, Helmert S, Michalski F, Werth S, et al. Coagulation and Fibrinolysis Effectiveness and safety of rivaroxaban therapy in daily-care patients with atrial fibrillation Results from the Dresden NOAC Registry. Thromb Haemost. 2016;1155:1–11. Hecker J, Marten S, Keller L, Helmert S, Michalski F, Werth S, et al. Coagulation and Fibrinolysis Effectiveness and safety of rivaroxaban therapy in daily-care patients with atrial fibrillation Results from the Dresden NOAC Registry. Thromb Haemost. 2016;1155:1–11.
16.
go back to reference Bassand J-P, Accetta G, Camm AJ, Cools F, Fitzmaurice DA, Fox KAA, et al. Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF. Eur Heart J. 2016;37:2882–89. Bassand J-P, Accetta G, Camm AJ, Cools F, Fitzmaurice DA, Fox KAA, et al. Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF. Eur Heart J. 2016;37:2882–89.
17.
go back to reference Fang MC, Go AS, Chang Y, Borowsky LH, Pomernacki NK, Udaltsova N, et al. Warfarin discontinuation after starting warfarin for atrial fibrillation. Circ Cardiovasc Qual Outcomes. 2010;3:624–31.CrossRefPubMedPubMedCentral Fang MC, Go AS, Chang Y, Borowsky LH, Pomernacki NK, Udaltsova N, et al. Warfarin discontinuation after starting warfarin for atrial fibrillation. Circ Cardiovasc Qual Outcomes. 2010;3:624–31.CrossRefPubMedPubMedCentral
18.
go back to reference Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation. 2007;115:2689–96.CrossRefPubMed Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation. 2007;115:2689–96.CrossRefPubMed
19.
go back to reference Beyer-Westendorf J, Förster K, Ebertz F, Gelbricht V, Schreier T, Göbelt M, et al. Drug persistence with rivaroxaban therapy in atrial fibrillation patients - Results from the Dresden non-interventional oral anticoagulation registry. Europace. 2015;17:530–8.CrossRefPubMedPubMedCentral Beyer-Westendorf J, Förster K, Ebertz F, Gelbricht V, Schreier T, Göbelt M, et al. Drug persistence with rivaroxaban therapy in atrial fibrillation patients - Results from the Dresden non-interventional oral anticoagulation registry. Europace. 2015;17:530–8.CrossRefPubMedPubMedCentral
20.
go back to reference Nührich JM, Kuck KH, Andresen D, Steven D, Spitzer SG, Hoffmann E, et al. Oral anticoagulation is frequently discontinued after ablation of paroxysmal atrial fibrillation despite previous stroke: data from the German Ablation Registry. Clin Res Cardiol. 2015;104:463–70.CrossRefPubMed Nührich JM, Kuck KH, Andresen D, Steven D, Spitzer SG, Hoffmann E, et al. Oral anticoagulation is frequently discontinued after ablation of paroxysmal atrial fibrillation despite previous stroke: data from the German Ablation Registry. Clin Res Cardiol. 2015;104:463–70.CrossRefPubMed
21.
go back to reference Beyer-Westendorf J, Ehlken B, Evers T. Real-world persistence and adherence to oral anticoagulation for stroke risk reduction in patients with atrial fibrillation. Europace. 2016;18:1150–7. Beyer-Westendorf J, Ehlken B, Evers T. Real-world persistence and adherence to oral anticoagulation for stroke risk reduction in patients with atrial fibrillation. Europace. 2016;18:1150–7.
22.
go back to reference Martinez C, Katholing A, Wallenhorst C, Freedman SB. Therapy persistence in newly diagnosed non-valvular atrial fibrillation treated with warfarin or NOAC: A cohort study. Thromb Haemost. 2016;115:31–9.CrossRefPubMed Martinez C, Katholing A, Wallenhorst C, Freedman SB. Therapy persistence in newly diagnosed non-valvular atrial fibrillation treated with warfarin or NOAC: A cohort study. Thromb Haemost. 2016;115:31–9.CrossRefPubMed
Metadata
Title
Thromboembolic events, bleeding, and drug discontinuation in patients with atrial fibrillation on anticoagulation: a prospective hospital-based registry
Authors
Oliver Königsbrügge
Alexander Simon
Hans Domanovits
Ingrid Pabinger
Cihan Ay
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2016
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-016-0438-5

Other articles of this Issue 1/2016

BMC Cardiovascular Disorders 1/2016 Go to the issue