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DOI: 10.1055/a-0593-3513
Gerinnungshemmende Therapie
Haben die direkten oralen Antikoagulanzien die Vitamin-K-Antagonisten „verbessert“?Publication History
Publication Date:
09 May 2018 (online)
Zusammenfassung
Eine gerinnungshemmende Therapie mit Vitamin-K-Antagonisten erfordert eine individuelle Dosisfindung und eine ständige Therapiekontrolle.
Die Wirkdauer insbesondere von Phenprocoumon ist mit bis zu 21 Tagen sehr lang und nicht vorhersehbar und verkürzt sich nach Vitamin-K-Gabe auf 2 Tage, es besteht ein erhebliches Blutungsrisiko und der Schweregrad der Blutungen ist in der Regel höher als bei vergleichbaren Blutungen unter direkten oralen Antikoagulanzien (DOAK). Für operative Eingriffe müssen Vitamin-K-Antagonisten meist abgesetzt werden, die Empfehlungen einer präoperativen 5-tägigen Therapiepause ohne Überbrückung durch ein niedermolekulares Heparin für Warfarin sind auf Phenprocoumon nicht übertragbar. Bei Absetzen von DOAK wird eine normale Hämostasefunktion hingegen in der Regel innerhalb von 24–48 Stunden erreicht. Längerfristige Behandlung mit Vitamin-K-Antagonisten führt häufig zu Osteoporose und vermehrter Atherosklerose, sowie zu zunehmender Beeinträchtigung der Nierenfunktion, Effekte, die unter DOAK nicht beobachtet werden.
Spezielle Probleme für Vitamin K-Antagonisten ergeben sich bei Patienten mit Antiphospholipid-Syndrom, Protein C-Mangel, Protein S-Mangel oder Faktor VII-Mangel. Für eine bevorzugte Verwendung von DOAK sprechen rascher Wirkbeginn, kurze und vorhersehbare Wirkdauer bei standardisierter Dosierung, weniger und weniger schwere Blutungen, wesentlich einfacheres perioperatives Management und Vermeidung von Osteoporose und anderen Folgen der Vitamin-K-Antagonisten. Für die zugelassenen Indikationen haben DOAK daher etliche Vorteile im Vergleich zu den Vitamin-K-Antagonisten. Es ist aber zu berücksichtigen, dass auch bei Verwendung von DOAK eine gewissenhafte ärztliche Patientenführung nötig ist und die DOAK für einige Indikationen nicht zugelassen sind.
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Literatur
- 1 Koller F, Jakob H. [A new highly active anticoagulant with prolonged effect (marcoumar)]. Schweiz Med Wochenschr 1953; 83: 476-479
- 2 Jurgens R. [Experimental research on the anticoagulant marcoumar (3-(1-phenyl-propyl)-4-hydroxy-coumarin) and its antagonist konakion (synthetic vitamin K1)]. Schweiz Med Wochenschr 1953; 83: 471-475
- 3 Deutsch E, Hueber EF, Mayer E. et al. [The therapeutic use of a new anticoagulant, marcoumar]. Klin Med Osterr Z Wiss Prakt Med 1954; 9: 49-60
- 4 Abduljalil K, Lazar S, Natanzon M. et al. Quantifying the effect of covariates on concentrations and effects of steady-state phenprocoumon using a population pharmacokinetic/pharmacodynamic model. Clin Pharmacokinet 2013; 52: 359-371
- 5 Verhoef TI, Redekop WK, Daly AK. et al. Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon. Br J Clin Pharmacol 2014; 77: 626-641
- 6 Lubetsky A, Yonath H, Olchovsky D. et al. Comparison of oral vs intravenous phytonadione (vitamin K1) in patients with excessive anticoagulation: a prospective randomized controlled study. Arch Intern Med 2003; 163: 2469-2473
- 7 Penning-van Beest FJ, Rosendaal FR, Grobbee DE. et al. Course of the international Normalized Ratio in response to oral vitamin K1 in patients overanticoagulated with phenprocoumon. Br J Haematol 1999; 104: 241-245
- 8 Lorenz R, Kienast J, Otto U. et al. Successful emergency reversal of phenprocoumon anticoagulation with prothrombin complex concentrate: a prospective clinical study. Blood Coagul Fibrinolysis 2007; 18: 565-570
- 9 Almutairi AR, Zhou L, Gellad WF. et al. Effectiveness and Safety of Non-vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation and Venous Thromboembolism: A Systematic Review and Meta-analyses. Clin Ther 2017; 39: 1456-1478 e1436
- 10 Becattini C, Franco L, Beyer-Westendorf J. et al. Major bleeding with vitamin K antagonists or direct oral anticoagulants in real-life. Int J Cardiol 2017; 227: 261-266
- 11 Chatterjee S, Sardar P, Biondi-Zoccai G. et al. New oral anticoagulants and the risk of intracranial hemorrhage: traditional and Bayesian meta-analysis and mixed treatment comparison of randomized trials of new oral anticoagulants in atrial fibrillation. JAMA Neurol 2013; 70: 1486-1490
- 12 Esteve-Pastor MA, Rivera-Caravaca JM, Roldan V. et al. Estimated absolute effects on efficacy and safety outcomes of using non-vitamin K antagonist oral anticoagulants in ‚real-world‘ atrial fibrillation patients: A comparison with optimally acenocoumarol anticoagulated patients. Int J Cardiol 2018; 254: 125-131
- 13 Hohnloser SH, Basic E, Hohmann C. et al. Effectiveness and Safety of Non-Vitamin K Oral Anticoagulants in Comparison to Phenprocoumon: Data from 61,000 Patients with Atrial Fibrillation. Thromb Haemost. 2018 doi: 10.1160/TH17–10–0733. [Epub ahead of print]
- 14 Kobayashi L, Barmparas G, Bosarge P. et al. Novel oral anticoagulants and trauma: The results of a prospective American Association for the Surgery of Trauma Multi-Institutional Trial. J Trauma Acute Care Surg 2017; 82: 827-835
- 15 Saji N, Kimura K, Aoki J. et al. Intracranial Hemorrhage Caused by Non-Vitamin K Antagonist Oral Anticoagulants (NOACs)- Multicenter Retrospective Cohort Study in Japan. Circ J 2015; 79: 1018-1023
- 16 Lopes RD, Guimaraes PO, Kolls BJ. et al. Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation therapy. Blood 2017; 129: 2980-2987
- 17 Caldeira D, Barra M, Ferreira A. et al. Systematic review with meta-analysis: the risk of major gastrointestinal bleeding with non-vitamin K antagonist oral anticoagulants. Aliment Pharmacol Ther 2015; 42: 1239-1249
- 18 Sherwood MW, Nessel CC, Hellkamp AS. et al. Gastrointestinal Bleeding in Patients With Atrial Fibrillation Treated With Rivaroxaban or Warfarin: ROCKET AF Trial. J Am Coll Cardiol 2015; 66: 2271-2281
- 19 Takahashi H, Jimbo Y, Takano H. et al. Intracerebral Hematoma Occurring During Warfarin Versus Non-Vitamin K Antagonist Oral Anticoagulant Therapy. Am J Cardiol 2016; 118: 222-225
- 20 Adachi T, Hoshino H, Takagi M. et al. Volume and Characteristics of Intracerebral Hemorrhage with Direct Oral Anticoagulants in Comparison with Warfarin. Cerebrovasc Dis Extra 2017; 7: 62-71
- 21 Berger R, Salhanick SD, Chase M. et al. Hemorrhagic complications in emergency department patients who are receiving dabigatran compared with warfarin. Ann Emerg Med 2013; 61: 475-479
- 22 Eerenberg ES, Middeldorp S, Levi M. et al. Clinical impact and course of major bleeding with rivaroxaban and vitamin K antagonists. J Thromb Haemost 2015; 13: 1590-1596
- 23 Brekelmans MP, Bleker SM, Bauersachs R. et al. Clinical impact and course of major bleeding with edoxaban versus vitamin K antagonists. Thromb Haemost 2016; 116: 155-161
- 24 Bleker SM, Brekelmans MPA, Eerenberg ES. et al. Clinical impact of major bleeding in patients with venous thromboembolism treated with factor Xa inhibitors or vitamin K antagonists. An individual patient data meta-analysis. Thromb Haemost 2017; 117: 1944-1951
- 25 Brodie MM, Newman JC, Smith T. et al. Severity of Gastrointestinal Bleeding in Patients Treated with Direct-Acting Oral Anticoagulants. Am J Med. 2017 doi: 10.1016/j.amjmed.2017.11.007. [Epub ahead of print]
- 26 Feeney JM, Santone E, DiFiori M. et al. Compared to warfarin, direct oral anticoagulants are associated with lower mortality in patients with blunt traumatic intracranial hemorrhage: A TQIP study. J Trauma Acute Care Surg 2016; 81: 843-848
- 27 Pietschmann P, Woloszczuk W, Panzer S. et al. Decreased serum osteocalcin levels in phenprocoumon-treated patients. J Clin Endocrinol Metab 1988; 66: 1071-1074
- 28 Donaldson CJ, Harrington DJ. Therapeutic warfarin use and the extrahepatic functions of vitamin K-dependent proteins. Br J Biomed Sci 2017; 74: 163-169
- 29 Rezaieyazdi Z, Falsoleiman H, Khajehdaluee M. et al. Reduced bone density in patients on long-term warfarin. Int J Rheum Dis 2009; 12: 130-135
- 30 Cheng HY. The association of warfarin use with osteoporotic fracture in elderly patients with atrial fibrillation. Arch Intern Med 2006; 166: 1525 author reply 1525
- 31 Namba S, Yamaoka-Tojo M, Hashikata T. et al. Long-term warfarin therapy and biomarkers for osteoporosis and atherosclerosis. BBA Clin 2015; 4: 76-80
- 32 Abdulameer AH, Sulaiman S, Kader M. An Assessment of Osteoporotic Conditions among Users and Non-Users of Warfarin: A Case-Control Study. J Clin Diagn Res 2017; 11: Oc21-oc24
- 33 Avila ML, Pullenayegum E, Williams S. et al. Timing of low bone mineral density and predictors of bone mineral density trajectory in children on long-term warfarin: a longitudinal study. Osteoporos Int 2016; 27: 1547-1557
- 34 Barnes C, Newall F, Ignjatovic V. et al. Reduced bone density in children on long-term warfarin. Pediatr Res 2005; 57: 578-581
- 35 Namba S, Yamaoka-Tojo M, Kakizaki R. et al. Effects on bone metabolism markers and arterial stiffness by switching to rivaroxaban from warfarin in patients with atrial fibrillation. Heart Vessels 2017; 32: 977-982
- 36 Lau WC, Chan EW, Cheung CL. et al. Association Between Dabigatran vs Warfarin and Risk of Osteoporotic Fractures Among Patients With Nonvalvular Atrial Fibrillation. Jama 2017; 317: 1151-1158
- 37 Szummer K, Gasparini A, Eliasson S. et al. Time in Therapeutic Range and Outcomes After Warfarin Initiation in Newly Diagnosed Atrial Fibrillation Patients With Renal Dysfunction. J Am Heart Assoc. 2017 6.
- 38 Van Der Meersch H, De Bacquer D, De Vriese AS. Vitamin K antagonists for stroke prevention in hemodialysis patients with atrial fibrillation: A systematic review and meta-analysis. Am Heart J 2017; 184: 37-46
- 39 Wong CX, Odutayo A, Emdin CA. et al. Meta-Analysis of Anticoagulation Use, Stroke, Thromboembolism, Bleeding, and Mortality in Patients With Atrial Fibrillation on Dialysis. Am J Cardiol 2016; 117: 1934-1941
- 40 Tan J, Liu S, Segal JB. et al. Warfarin use and stroke, bleeding and mortality risk in patients with end stage renal disease and atrial fibrillation: a systematic review and meta-analysis. BMC Nephrol 2016; 17: 157
- 41 Tan J, Bae S, Segal JB. et al. Warfarin Use And the Risk Of Stroke, Bleeding, And Mortality In Older Adults On Dialysis With Incident Atrial Fibrillation. Nephrology (Carlton). 2017
- 42 Yao X, Tangri N, Gersh BJ. et al. Renal Outcomes in Anticoagulated Patients With Atrial Fibrillation. J Am Coll Cardiol 2017; 70: 2621-2632
- 43 Pelliccia F, Rosanio S, Marazzi G. et al. Efficacy and safety of novel anticoagulants versus vitamin K antagonists in patients with mild and moderate to severe renal insufficiency: Focus on apixaban. Int J Cardiol 2016; 225: 77-81
- 44 Chang M, Yu Z, Shenker A. et al. Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of apixaban. J Clin Pharmacol 2016; 56: 637-645
- 45 Stanton BE, Barasch NS, Tellor KB. Comparison of the Safety and Effectiveness of Apixaban versus Warfarin in Patients with Severe Renal Impairment. Pharmacotherapy 2017; 37: 412-419
- 46 Di Lullo L, Ronco C, Cozzolino M. et al. Nonvitamin K-dependent oral anticoagulants (NOACs) in chronic kidney disease patients with atrial fibrillation. Thromb Res 2017; 155: 38-47
- 47 Della Valle P, Crippa L, Safa O. et al. Potential failure of the International Normalized Ratio (INR) System in the monitoring of oral anticoagulation in patients with lupus anticoagulants. Ann Med Interne (Paris) 1996; 147 (Suppl. 01) 10-14
- 48 Crowl A, Schullo-Feulner A, Moon JY. Warfarin monitoring in antiphospholipid syndrome and lupus anticoagulant. Ann Pharmacother 2014; 48: 1479-1483