Sicherheit und Effektivität der oralen Antikoagulation bei Vorhofflimmern und Niereninsuffizienz im Praxisalltag

Zusammenfassung

Die momentanen Leitlinien empfehlen Nicht-Vitamin-K-abhängige orale Antikoagulanzien (NOAK) als Therapiestandard für die Schlaganfallprophylaxe bei Patienten mit Vorhofflimmern (VHF) und sind daher den Vitamin-K-Antagonisten (VKA) vorzuziehen. Diese Empfehlung gilt auch für Patienten mit VHF und chronischer nicht dialysepflichtiger Niereninsuffizienz. Sogenannte Real-World-Evidenz (RWE), also Daten aus der klinischen Praxis, erweitert und bestätigt die zugrunde liegende klinische Evidenz, die in den stärker formalisierten klinischen Prüfungen mit NOAK und VKA, hier ausschließlich Warfarin, gewonnen wurde. Darüber hinaus zeigte die RWE, dass die Überlegenheit der NOAK gegenüber dem VKA Warfarin auch für Phenprocoumon gilt, dem in Deutschland gebräuchlichsten VKA. Auch fanden sich Hinweise, dass bei Patienten mit chronischen Nierenerkrankungen das Fortschreiten der Nierenfunktionsstörung unter Behandlung mit NOAK geringer ausfallen kann als unter VKA.

Abstract

Non-vitamin-K dependent oral anti-coagulants (NOAC) are the current therapeutic standard for preventing strokes in patients with atrial fibrillation (AF) and should be preferred over vitamin K antagonists (VKA) in this indication. This recommendation applies also to patients with VHF and concomitant chronic kidney disease (CKD). Real World Evidence (RWE), i. e., structured data from clinical practice, extends and confirms the clinical evidence generated in more formalized clinical trials with NOAC and VKA. In addition, RWE in respect to the indication showed that the superiority of NOAC versus the VKA warfarin can also be extrapolated to phenprocoumon, the commonly used VKA in Germany. Furthermore, data include evidence that the typical progression of CKD appears to be less pronounced in individuals treated with NOAC compared to those treated with VKA.

Schlüsselwörter

NOAK - Phenprocoumon - Nierenversagen - Progression - Praxisdaten

Key words

NOAC - phenprocoumon - CKD - progression - real-world evidence

Publication History

Article published online:
11 May 2022

• Literatur

• 1 Hindricks G, Potpara T, Dagres N. et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2021; 42: 373-498 DOI: 10.1093/eurheartj/ehaa612.
• 2 Wilke T, Groth A, Mueller S. et al. Incidence and prevalence of atrial fibrillation: an analysis based on 8.3 million patients. Eur Eur Pacing Arrhythm Card Electrophysiol J Work Groups Card Pacing Arrhythm Card Cell Electrophysiol Eur Soc Cardiol 2013; 15: 486-493 DOI: 10.1093/europace/eus333.
• 3 Steffel J, Verhamme P, Potpara TS. et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 2018; 39: 1330-1393 DOI: 10.1093/eurheartj/ehy136.
• 4 Turakhia MP, Blankestijn PJ, Carrero J-J. et al. Chronic kidney disease and arrhythmias: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Eur Heart J 2018; 39: 2314-2325 DOI: 10.1093/eurheartj/ehy060.
• 5 KDIGO. CKD Evaluation and Management – KDIGO. Im Internet (Stand: 16.05.2021): https://kdigo.org/guidelines/ckd-evaluation-and-management/
• 6 Girndt M, Trocchi P, Scheidt-Nave C. et al. The Prevalence of Renal Failure. Results from the German Health Interview and Examination Survey for Adults, 2008–2011 (DEGS1). Dtsch Arzteblatt Int 2016; 113: 85-91 DOI: 10.3238/arztebl.2016.0085.
• 7 Pecoits-Filho R, Abensur H, Betônico CCR. et al. Interactions between kidney disease and diabetes: dangerous liaisons. Diabetol Metab Syndr 2016; 8: 50 DOI: 10.1186/s13098-016-0159-z.
• 8 ERA-EDTA Registry Annual Report 2013 | GHDx. Im Internet (Stand: 16.05.2021): http://ghdx.healthdata.org/record/era-edta-registry-annual-report-2013
• 9 Piccini JP, Stevens SR, Chang Y. et al. Renal dysfunction as a predictor of stroke and systemic embolism in patients with nonvalvular atrial fibrillation: validation of the R(2)CHADS(2) index in the ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation) study cohorts. Circulation 2013; 127: 224-232 DOI: 10.1161/CIRCULATIONAHA.112.107128.
• 10 Goto S, Angchaisuksiri P, Bassand J-P. et al. Management and 1-Year Outcomes of Patients With Newly Diagnosed Atrial Fibrillation and Chronic Kidney Disease: Results From the Prospective GARFIELD – AF Registry. J Am Heart Assoc 2019; 8: e010510 DOI: 10.1161/JAHA.118.010510.
• 11 Zeymer U, Bonnemeier H, Wanner C. [Anticoagulation in patients with non-valvular atrial fibrillation (nvAF) and chronic kidney disease (CKD)]. Dtsch Med Wochenschr 1946 2019; 144: 1642-1649 DOI: 10.1055/a-1008-5548.
• 12 Kumar S, Lim E, Covic A. et al. Anticoagulation in Concomitant Chronic Kidney Disease and Atrial Fibrillation: JACC Review Topic of the Week. J Am Coll Cardiol 2019; 74: 2204-2215 DOI: 10.1016/j.jacc.2019.08.1031.
• 13 Kimachi M, Furukawa TA, Kimachi K. et al. Direct oral anticoagulants versus warfarin for preventing stroke and systemic embolic events among atrial fibrillation patients with chronic kidney disease. Cochrane Database Syst Rev 2017; 11: CD011373 DOI: 10.1002/14651858.CD011373.pub2.
• 14 FDA Commissioner S and R. Real-World Evidence. FDA 2020. Im Internet (Stand: 16.05.2021): https://www.fda.gov/science-research/science-and-research-special-topics/real-world-evidence
• 15 European Medicines Agency. Guideline on registry-based studies. Draft. EMA/502388/2020 2020
• 16 Schrappe M. Versorgungsforschung – die langfristige Perspektive gestalten. GGW 2017; 17: 16-22
• 17 Willems BAG, Vermeer C, Reutelingsperger CPM. et al. The realm of vitamin K dependent proteins: Shifting from coagulation toward calcification. Mol Nutr Food Res 2014; 58: 1620-1635 DOI: 10.1002/mnfr.201300743.
• 18 van Gorp R, Schurgers L. New Insights into the Pros and Cons of the Clinical Use of Vitamin K Antagonists (VKAs) Versus Direct Oral Anticoagulants (DOACs). Nutrients 2015; 7: 9538-9557 DOI: 10.3390/nu7115479.
• 19 Coleman CI, Kreutz R, Sood N. et al. Rivaroxaban’s Impact on Renal Decline in Patients With Nonvalvular Atrial Fibrillation: A US MarketScan Claims Database Analysis. Clin Appl Thromb 2019; 25: 107602961986853 DOI: 10.1177/1076029619868535.
• 20 Yao X, Tangri N, Gersh BJ. et al. Renal Outcomes in Anticoagulated Patients With Atrial Fibrillation. J Am Coll Cardiol 2017; 70: 2621-2632 DOI: 10.1016/j.jacc.2017.09.1087.
• 21 Vaitsiakhovich T, Coleman C, Kleinjung F. et al. Clinical outcomes among non-valvular atrial fibrillation patients with renal dysfunction treated with warfarin or reduced dose rivaroxaban (AS25-60). Eur Stroke J 2019; 4: 150-276 DOI: 10.1177/2396987319845581.
• 22 Vaitsiakhovich T, Coleman CI, Kleinjung F. et al. P4746 Worsening of renal function in atrial fibrillation patients with stage 3 or 4 chronic kidney disease treated with warfarin or rivaroxaban – evidence from the real-world CALLIPER study in the US claims. Eur Heart J 2019; 40 DOI: 10.1093/eurheartj/ehz745.1122.
• 23 Hernandez AV, Bradley G, Khan M. et al. Rivaroxaban vs. warfarin and renal outcomes in non-valvular atrial fibrillation patients with diabetes. Eur Heart J – Qual Care Clin Outcomes 2020; 6: 301-307 DOI: 10.1093/ehjqcco/qcz047.
• 24 Coleman CI, Kreutz R, Sood NA. et al. Rivaroxaban Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation and Severe Kidney Disease or Undergoing Hemodialysis. Am J Med 2019; 132: 1078-1083 DOI: 10.1016/j.amjmed.2019.04.013.
• 25 Langer E, Ziemer S. [Established anticoagulants in secondary haemostasis--Vitamin K antagonists, heparins]. Hamostaseologie 2009; 29: 241-246
• 26 Ufer M. Comparative Pharmacokinetics of Vitamin K Antagonists: Warfarin, Phenprocoumon and Acenocoumarol. Clin Pharmacokinet 2005; 44: 1227-1246 DOI: 10.2165/00003088-200544120-00003.
• 27 Bonnemeier H, Huelsebeck M, Kloss S. Comparative effectiveness of rivaroxaban versus a vitamin K antagonist in patients with renal impairment treated for non-valvular atrial fibrillation in Germany – A retrospective cohort study. Int J Cardiol Heart Vasc 2019; 23: 100367 DOI: 10.1016/j.ijcha.2019.100367.
• 28 Bonnemeier H, Kreutz R, Kloss S. et al. Comparative safety and effectiveness of non-vitamin-K oral anticoagulants vs phenprocoumon in patients with non-valvular atrial fibrillation and renal disease – results from the RELOADED study (AS25-066). Eur Stroke J 2019; 4: 150-276 DOI: 10.1177/2396987319845581.
• 29 Bonnemeier H, Kreutz R, Enders D. et al. P4749 Renal function worsening in factor-xa inhibitors vs phenprocoumon in patients with non-valvular atrial fibrillation and renal disease – insights from the RELOADED study. Eur Heart J 2019; 40 DOI: 10.1093/eurheartj/ehz745.1125.
• 30 Lip GYH, Banerjee A, Boriani G. et al. Antithrombotic Therapy for Atrial Fibrillation: CHEST Guideline and Expert Panel Report. Chest 2018; 154: 1121-1201 DOI: 10.1016/j.chest.2018.07.040.
• 31 January CT, Wann LS, Calkins H. et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74: 104-132 DOI: 10.1016/j.jacc.2019.01.011.