Thromb Haemost 2018; 118(11): 1930-1939
DOI: 10.1055/s-0038-1673380
Stroke, Systemic or Venous Thromboembolism
Georg Thieme Verlag KG Stuttgart · New York

Management of Oral Anti-Coagulation in Patients with Heart Failure—Insights from the ThrombEVAL Study

Sebastian Göbel*
1   German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Mainz, Germany
2   Center for Cardiology – Cardiology I, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
,
Jürgen H. Prochaska*
1   German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Mainz, Germany
3   Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
4   Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
,
Lisa Eggebrecht
4   Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
,
Ronja Schmitz
4   Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
,
Claus Jünger
4   Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
,
Heidrun Lamparter
3   Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
4   Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
,
Markus Nagler
3   Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
4   Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
,
Karsten Keller
3   Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
,
Meike Coldewey
2   Center for Cardiology – Cardiology I, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
,
Sven-Oliver Tröbs
1   German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Mainz, Germany
2   Center for Cardiology – Cardiology I, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
,
Simon Diestelmeier
1   German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Mainz, Germany
2   Center for Cardiology – Cardiology I, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
,
Sören Schwuchow-Thonke
1   German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Mainz, Germany
2   Center for Cardiology – Cardiology I, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
,
Christoph Bickel
5   Department of Medicine I, Federal Armed Forces Central Hospital, Koblenz, Germany
,
Michael Lauterbach
6   Department of Medicine 3, Barmherzige Brüder Hospital Trier, Trier, Germany
,
Karl J. Lackner
1   German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Mainz, Germany
7   Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
,
Hugo ten Cate
3   Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
8   Thrombosis Center Maastricht, Cardiovascular Research Institute Maastricht and Maastricht University Medical Center, Maastricht University, Maastricht, The Netherlands
,
Thomas Münzel
1   German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Mainz, Germany
2   Center for Cardiology – Cardiology I, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
3   Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
,
Roland Hardt
9   Center for General Medicine and Geriatrics, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
,
Philipp S. Wild
1   German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Mainz, Germany
3   Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
4   Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany
› Author Affiliations
Funding This work was supported by grants of the state initiative ‘health economy’ of the Ministries of Health and Economics, Rhineland-Palatinate, Germany (grant identifier: AZ.623–1), the Federal Ministry of Education and Research, Germany (grant identifier: BMBF 10E01003), the Center for Translational Vascular Biology (CTVB) of the University Medical Center Mainz, Boehringer Ingelheim Pharma GmbH & Co. KG, Bayer Vital GmbH, Daiichi Sankyo Europe GmbH, Sanofi-Aventis Germany GmbH, IMO Institute GmbH, Portavita BV and the German Heart Foundation. The sponsoring bodies played no role in the planning, conduct or analysis of this investigator-initiated study.
Further Information

Publication History

23 March 2018

23 August 2018

Publication Date:
24 October 2018 (online)

Abstract

Patients with heart failure (HF) are frequently anti-coagulated with vitamin K-antagonists (VKAs). The use of long-acting VKA may be preferable for HF patients due to higher stability of plasma concentrations. However, evidence on phenprocoumon-based oral anti-coagulation (OAC) therapy in HF is scarce. The aim of this study was to assess the impact of the presence of HF on quality of phenprocoumon-based OAC and the subsequent clinical outcome. Quality of OAC therapy and the incidence of adverse events were analysed in a cohort of regular care (n = 2,011) from the multi-centre thrombEVAL study program (NCT01809015) stratified by the presence of HF. To assess the modifiability of outcome, results were compared with data from individuals receiving specialized care for anti-coagulation (n = 760). Overall, the sample comprised of 813 individuals with HF and 1,160 subjects without HF in the regular care cohort. Quality of OAC assessed by time in therapeutic range (TTR) was 66.1% (47.8%/82.8%) for patients with HF and 70.6% (52.1%/85.9%) for those without HF (p = 0.0046). Stratification for New York Heart Classification (NYHA)-class demonstrated a lower TTR with higher NYHA classes: TTRNYHA-I 69.6% (49.4%/85.6%), TTRNYHA-II 66.5% (50.1%/82.9%) and TTRNYHA-≥III 61.8% (43.1%/79.9%). This translated into a worse net clinical benefit outcome for HF (hazard ratio [HR] 1.63 [1.31/2.02]; p < 0.0001) and an increased risk of bleeding (HR 1.40 [1.04/1.89]; p = 0.028). Management in a specialized coagulation service resulted in an improvement of all, TTR (∆+12.5% points), anti-coagulation-specific and non-specific outcome of HF individuals. In conclusion, HF is an independent risk factor for low quality of OAC therapy translating into an increased risk for adverse events, which can be mitigated by specialized care.

* Sebastian Göbel and Jürgen H. Prochaska contributed equally to the study.


Supplementary Material

 
  • References

  • 1 Massie BM, Shah NB. Evolving trends in the epidemiologic factors of heart failure: rationale for preventive strategies and comprehensive disease management. Am Heart J 1997; 133 (06) 703-712
  • 2 Homma S, Thompson JL, Pullicino PM. , et al; WARCEF Investigators. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med 2012; 366 (20) 1859-1869
  • 3 Yancy CW, Jessup M, Bozkurt B. , et al; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 62 (16) e147-e239
  • 4 Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e44S-e88S
  • 5 Santhanakrishnan R, Wang N, Larson MG. , et al. Atrial fibrillation begets heart failure and vice versa: temporal associations and differences in preserved versus reduced ejection fraction. Circulation 2016; 133 (05) 484-492
  • 6 Eek AK, Øie E, Granas AG. Prescribing of NOACs has outnumbered warfarin: exploring how physicians choose anticoagulant treatments. Eur J Clin Pharmacol 2018; 74 (03) 323-330
  • 7 Nielsen PB, Skjøth F, Søgaard M, Kjældgaard JN, Lip GY, Larsen TB. Effectiveness and safety of reduced dose non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ 2017; 356: j510
  • 8 Forman DE, Butler J, Wang Y. , et al. Incidence, predictors at admission, and impact of worsening renal function among patients hospitalized with heart failure. J Am Coll Cardiol 2004; 43 (01) 61-67
  • 9 Holbrook A, Schulman S, Witt DM. , et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e152S-e184S
  • 10 Visser LE, Bleumink GS, Trienekens PH, Vulto AG, Hofman A, Stricker BH. The risk of overanticoagulation in patients with heart failure on coumarin anticoagulants. Br J Haematol 2004; 127 (01) 85-89
  • 11 Penning-van Beest FJ, van Meegen E, Rosendaal FR, Stricker BH. Characteristics of anticoagulant therapy and comorbidity related to overanticoagulation. Thromb Haemost 2001; 86 (02) 569-574
  • 12 van Walraven C, Jennings A, Oake N, Fergusson D, Forster AJ. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest 2006; 129 (05) 1155-1166
  • 13 Prochaska JH, Göbel S, Keller K. , et al. e-Health-based management of patients receiving oral anticoagulation therapy: results from the observational thrombEVAL study. J Thromb Haemost 2017; 15 (07) 1375-1385
  • 14 Prochaska JH, Coldewey M, Göbel S. , et al; thrombEVAL Study Group. Evaluation of oral anticoagulation therapy: rationale and design of the thrombEVAL study programme. Eur J Prev Cardiol 2015; 22 (05) 622-628
  • 15 Rosendaal FR, Cannegieter SC, van der Meer FJ, Briët E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993; 69 (03) 236-239
  • 16 Reynolds MW, Fahrbach K, Hauch O. , et al. Warfarin anticoagulation and outcomes in patients with atrial fibrillation: a systematic review and metaanalysis. Chest 2004; 126 (06) 1938-1945
  • 17 Covert DF. Vitamin K control of the increased hypoprothrombinemic effect of dicumarol in congestive heart failure. Am J Med Sci 1952; 224 (04) 439-445
  • 18 Kim EJ, Ozonoff A, Hylek EM. , et al. Predicting outcomes among patients with atrial fibrillation and heart failure receiving anticoagulation with warfarin. Thromb Haemost 2015; 114 (01) 70-77
  • 19 Stats D, Davison S. The increased hypoprothrombinemic effect of a small dose of dicumarol in congestive heart failure. Am J Med Sci 1949; 218 (03) 318-323
  • 20 Killip III T, Payne MA. High serum transaminase activity in heart disease. Circulatory failure and hepatic necrosis. Circulation 1960; 21: 646-660
  • 21 Safran AP, Schaffner F. Chronic passive congestion of the liver in man. Electron microscopic study of cell atrophy and intralobular fibrosis. Am J Pathol 1967; 50 (03) 447-463
  • 22 Allen LA, Felker GM, Pocock S. , et al; CHARM Investigators. Liver function abnormalities and outcome in patients with chronic heart failure: data from the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program. Eur J Heart Fail 2009; 11 (02) 170-177
  • 23 Proietti M, Raparelli V, Olshansky B, Lip GY. Polypharmacy and major adverse events in atrial fibrillation: observations from the AFFIRM trial. Clin Res Cardiol 2016; 105 (05) 412-420
  • 24 Samsa GP, Matchar DB, Goldstein LB. , et al. Quality of anticoagulation management among patients with atrial fibrillation: results of a review of medical records from 2 communities. Arch Intern Med 2000; 160 (07) 967-973
  • 25 Homma S, Thompson JL, Qian M. , et al; WARCEF Investigators. Quality of anticoagulation control in preventing adverse events in patients with heart failure in sinus rhythm: Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial substudy. Circ Heart Fail 2015; 8 (03) 504-509
  • 26 Beton O, Asarcikli LD, Sen T. , et al. Right ventricular dysfunction complicates time in therapeutic range in heart failure patients receiving warfarin. Pharmacology 2017; 99 (1-2): 19-26
  • 27 van Diepen S, Hellkamp AS, Patel MR. , et al. Efficacy and safety of rivaroxaban in patients with heart failure and nonvalvular atrial fibrillation: insights from ROCKET AF. Circ Heart Fail 2013; 6 (04) 740-747
  • 28 Gadisseur AP, van der Meer FJ, Adriaansen HJ, Fihn SD, Rosendaal FR. Therapeutic quality control of oral anticoagulant therapy comparing the short-acting acenocoumarol and the long-acting phenprocoumon. Br J Haematol 2002; 117 (04) 940-946
  • 29 Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (6, Suppl): 160S-198S
  • 30 Khazanie P, Liang L, Qualls LG. , et al. Outcomes of Medicare beneficiaries with heart failure and atrial fibrillation. JACC Heart Fail 2014; 2 (01) 41-48
  • 31 Anand IS, Kempf T, Rector TS. , et al. Serial measurement of growth-differentiation factor-15 in heart failure: relation to disease severity and prognosis in the Valsartan Heart Failure Trial. Circulation 2010; 122 (14) 1387-1395
  • 32 Miller WL, Hartman KA, Burritt MF, Grill DE, Jaffe AS. Profiles of serial changes in cardiac troponin T concentrations and outcome in ambulatory patients with chronic heart failure. J Am Coll Cardiol 2009; 54 (18) 1715-1721
  • 33 Opasich C, Cazzola M, Scelsi L. , et al. Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure. Eur Heart J 2005; 26 (21) 2232-2237