Özel Popülasyonlarda Oral Antikoagülan Tedavi: Yaşlı, Obez ve Kronik Karaciğer Yetmezliği Olan Hastalarda Güncel Yaklaşımlar

Yazarlar

Kadir Köseoğlu
Sena Güzel Karahan

Özet

Referanslar

WHO. Noncommunicable diseases. 31.08.2025 tarihinde https://www.who.int/health-topics/noncommunicable-diseases#tab=tab_1 adresinden ulaşılmıştır.

Weitz JI, Chan NC. Advances in Antithrombotic Therapy. Arterioscler Thromb Vasc Biol. 2019;39(1):7-12. doi:10.1161/ATVBAHA.118.310960.

Saha P, Humphries J, Modarai B, et al. Leukocytes and the natural history of deep vein thrombosis: current concepts and future directions. Arterioscler Thromb Vasc Biol. 2011;31(3):506-512. doi:10.1161/ATVBAHA.110.213405

Kushner A, West WP, Khan Suheb MZ, Pillarisetty LS. Virchow Triad. In: StatPearls. Treasure Island (FL): StatPearls Publishing; June 7, 2024.

Lichota A, Szewczyk EM, Gwozdzinski K. Factors Affecting the Formation and Treatment of Thrombosis by Natural and Synthetic Compounds. Int J Mol Sci. 2020;21(21):7975. Published 2020 Oct 27. doi:10.3390/ijms21217975

Pastori D, Cormaci VM, Marucci S, et al. A Comprehensive Review of Risk Factors for Venous Thromboembolism: From Epidemiology to Pathophysiology. Int J Mol Sci. 2023;24(4):3169. Published 2023 Feb 5. doi:10.3390/ijms24043169

Anderson FA Jr, Spencer FA. Risk factors for venous thromboembolism. Circulation. 2003;107(23 Suppl 1):I9-I16. doi:10.1161/01.CIR.0000078469.07362.E6

Barco S, Woersching AL, Spyropoulos AC, Piovella F, Mahan CE. European Union-28: An annualised cost-of-illness model for venous thromboembolism. Thromb Haemost. 2016;115(4):800-808. doi:10.1160/TH15-08-0670

Barco S, Mahmoudpour SH, Valerio L, et al. Trends in mortality related to pulmonary embolism in the European Region, 2000-15: analysis of vital registration data from the WHO Mortality Database. Lancet Respir Med. 2020;8(3):277-287. doi:10.1016/S2213-2600(19)30354-6

Kholmukhamedov A, Subbotin D, Gorin A, Ilyassov R. Anticoagulation Management: Current Landscape and Future Trends. J Clin Med. 2025;14(5):1647. Published 2025 Feb 28. doi:10.3390/jcm14051647

Pirmohamed M, Kamali F, Daly AK, Wadelius M. Oral anticoagulation: a critique of recent advances and controversies. Trends Pharmacol Sci. 2015;36(3):153-163. doi:10.1016/j.tips.2015.01.003

Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962. doi:10.1016/S0140-6736(13)62343-0

Wang TY, Magid DJ, Ting HH, et al. The quality of antiplatelet and anticoagulant medication administration among ST-segment elevation myocardial infarction patients transferred for primary percutaneous coronary intervention. Am Heart J. 2014;167(6):833-839. doi:10.1016/j.ahj.2014.03.002

Kitchen S, Gray E, Mackie I, Baglin T, Makris M; BCSH committee. Measurement of non-coumarin anticoagulants and their effects on tests of Haemostasis: Guidance from the British Committee for Standards in Haematology. Br J Haematol. 2014;166(6):830-841. doi:10.1111/bjh.12975

Rogula S, Gąsecka A, Mazurek T, Navarese EP, Szarpak Ł, Filipiak KJ. Safety and Efficacy of DOACs in Patients with Advanced and End-Stage Renal Disease. Int J Environ Res Public Health. 2022;19(3):1436. Published 2022 Jan 27. doi:10.3390/ijerph19031436

Heeringa J, van der Kuip DA, Hofman A, et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J. 2006;27(8):949-953. doi:10.1093/eurheartj/ehi825

Chen Q, Lapane K, Nunes AP, Tjia J, Hugunin J, Alcusky M. Prevalence and the factors associated with oral anticoagulant use among nursing home residents. J Clin Pharm Ther. 2021;46(6):1714-1728. doi:10.1111/jcpt.13508

Turnheim K. When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly. Exp Gerontol. 2003;38(8):843-853. doi:10.1016/s0531-5565(03)00133-5

Bendayan M, Mardigyan V, Williamson D, et al. Muscle Mass and Direct Oral Anticoagulant Activity in Older Adults With Atrial Fibrillation. J Am Geriatr Soc. 2021;69(4):1012-1018. doi:10.1111/jgs.16992

Stuby J, Haschke M, Tritschler T, Aujesky D. Oral anticoagulant therapy in older adults. Thromb Res. 2024;238:1-10. doi:10.1016/j.thromres.2024.04.009

Eliquis. Kısa Ürün Bilgisi. 31.08.2025 tarihinde https://labeling.pfizer.com/ShowLabeling.aspx?id=19195 adresinden ulaşılmıştır.

Lixiana. Kısa Ürün Bilgisi. 31.08.2025 tarihinde https://www.daiichi-sankyo.com.tr/fileadmin/daiichi-sankyo-contents/DS_TR/LIXIANA_30_MG_KUEB.pdf adresinden ulaşılmıştır.

Lane S, Al-Zubiedi S, Hatch E, et al. The population pharmacokinetics of R- and S-warfarin: effect of genetic and clinical factors. Br J Clin Pharmacol. 2012;73(1):66-76. doi:10.1111/j.1365-2125.2011.04051.x

Wynne H, Cope L, Kelly P, Whittingham T, Edwards C, Kamali F. The influence of age, liver size and enantiomer concentrations on warfarin requirements. Br J Clin Pharmacol. 1995;40(3):203-207.

Shendre A, Parmar GM, Dillon C, Beasley TM, Limdi NA. Influence of Age on Warfarin Dose, Anticoagulation Control, and Risk of Hemorrhage. Pharmacotherapy. 2018;38(6):588-596. doi:10.1002/phar.2089

Edwina AE, Dia N, Dreesen E, et al. Insights into the Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants in Older Adults with Atrial Fibrillation: A Structured Narrative Review. Clin Pharmacokinet. 2023;62(3):351-373. doi:10.1007/s40262-023-01222-w

Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381(9868):752-762. doi:10.1016/S0140-6736(12)62167-9

Mitnitski A, Rockwood K. The rate of aging: the rate of deficit accumulation does not change over the adult life span. Biogerontology. 2016;17(1):199-204. doi:10.1007/s10522-015-9583-y

Hoover M, Rotermann M, Sanmartin C, Bernier J. Validation of an index to estimate the prevalence of frailty among community-dwelling seniors. Health Rep. 2013;24(9):10-17.

Wilkinson C, Clegg A, Todd O, et al. Atrial fibrillation and oral anticoagulation in older people with frailty: a nationwide primary care electronic health records cohort study. Age Ageing. 2021;50(3):772-779. doi:10.1093/ageing/afaa265

Lutsey PL, Windham BG, Misialek JR, et al. Long-Term Association of Venous Thromboembolism With Frailty, Physical Functioning, and Quality of Life: The Atherosclerosis Risk in Communities Study. J Am Heart Assoc. 2020;9(12):e015656. doi:10.1161/JAHA.119.015656

Grymonprez M, Petrovic M, De Backer TL, Steurbaut S, Lahousse L. Impact of frailty on the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation: a nationwide cohort study. Eur Heart J Qual Care Clin Outcomes. 2024;10(1):55-65. doi:10.1093/ehjqcco/qcad019

Kim DH, Pawar A, Gagne JJ, et al. Frailty and Clinical Outcomes of Direct Oral Anticoagulants Versus Warfarin in Older Adults With Atrial Fibrillation : A Cohort Study. Ann Intern Med. 2021;174(9):1214-1223. doi:10.7326/M20-7141

Kok WE, Haverkort EB, Algra YA, et al. The association between polypharmacy and malnutrition(risk) in older people: A systematic review. Clin Nutr ESPEN. 2022;49:163-171. doi:10.1016/j.clnesp.2022.03.007

Shaikh F, Pasch LB, Newton PJ, Bajorek BV, Ferguson C. Addressing Multimorbidity and Polypharmacy in Individuals With Atrial Fibrillation. Curr Cardiol Rep. 2018;20(5):32. Published 2018 Mar 24. doi:10.1007/s11886-018-0975-x

Leiss W, Méan M, Limacher A, et al. Polypharmacy is associated with an increased risk of bleeding in elderly patients with venous thromboembolism. J Gen Intern Med. 2015;30(1):17-24. doi:10.1007/s11606-014-2993-8

Guthrie B, Makubate B, Hernandez-Santiago V, Dreischulte T. The rising tide of polypharmacy and drug-drug interactions: population database analysis 1995-2010. BMC Med. 2015;13:74. Published 2015 Apr 7. doi:10.1186/s12916-015-0322-7

Kumar S, Danik SB, Altman RK, et al. Non-Vitamin K Antagonist Oral Anticoagulants and Antiplatelet Therapy for Stroke Prevention in Patients With Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials. Cardiol Rev. 2016;24(5):218-223. doi:10.1097/CRD.0000000000000088

Valeriani E, Porreca E, Weitz JI, Schulman S, Candeloro M, Di Nisio M. Impact of concomitant antiplatelet therapy on the efficacy and safety of direct oral anticoagulants for acute venous thromboembolism: Systematic review and meta-analysis. J Thromb Haemost. 2020;18(7):1661-1671. doi:10.1111/jth.14807

Lee JY, Oh IY, Lee JH, et al. The increased risk of bleeding due to drug-drug interactions in patients administered direct oral anticoagulants. Thromb Res. 2020;195:243-249. doi:10.1016/j.thromres.2020.07.054

Eggebrecht L, Nagler M, Göbel S, et al. Relevance of Polypharmacy for Clinical Outcome in Patients Receiving Vitamin K Antagonists. J Am Geriatr Soc. 2019;67(3):463-470. doi:10.1111/jgs.15712

Martínez-Montesinos L, Rivera-Caravaca JM, Agewall S, et al. Polypharmacy and adverse events in atrial fibrillation: Main cause or reflection of multimorbidity?. Biomed Pharmacother. 2023;158:114064. doi:10.1016/j.biopha.2022.114064

Zheng Y, Li S, Liu X, Lip GYH, Guo L, Zhu W. Effect of Oral Anticoagulants in Atrial Fibrillation Patients with Polypharmacy: A Meta-analysis. Thromb Haemost. 2025;125(2):166-177. doi:10.1055/s-0043-1770724

Madhavan M, Graff-Radford J, Piccini JP, Gersh BJ. Cognitive dysfunction in atrial fibrillation. Nat Rev Cardiol. 2018;15(12):744-756. doi:10.1038/s41569-018-0075-z

Rahman AA, Michaud J, Dell'Aniello S, et al. Oral Anticoagulants and the Risk of Dementia in Patients With Nonvalvular Atrial Fibrillation: A Population-Based Cohort Study. Neurology. 2023;100(12):e1309-e1320. doi:10.1212/WNL.0000000000206748

Ferri C, Del Pinto R. Is there a connection among atrial fibrillation, anticoagulant treatment, and dementia?. Eur Heart J Suppl. 2020;22(Suppl E):E79-E81. doi:10.1093/eurheartj/suaa066

Rivard L, Friberg L, Conen D, et al. Atrial Fibrillation and Dementia: A Report From the AF-SCREEN International Collaboration. Circulation. 2022;145(5):392-409. doi:10.1161/CIRCULATIONAHA.121.055018

Andrade JG, Aguilar M, Atzema C, et al. The 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Comprehensive Guidelines for the Management of Atrial Fibrillation. Can J Cardiol. 2020;36(12):1847-1948. doi:10.1016/j.cjca.2020.09.001

National Institute for Health and Care Excellence (NICE). 2019 surveillance of falls in older people: assessing risk and prevention (NICE guideline CG161) [Internet]. 2019 surveillance of falls in older people: assessing risk and prevention (NICE guideline CG161) [Internet]. 2019 [cited 2025 Aug 27];(May). Available from: https://pubmed.ncbi.nlm.nih.gov/31869045/

Wilkinson C, Clegg A, Todd O, et al. Atrial fibrillation and oral anticoagulation in older people with frailty: a nationwide primary care electronic health records cohort study. Age Ageing. 2021;50(3):772-779. doi:10.1093/ageing/afaa265

Pugh D, Pugh J, Mead GE. Attitudes of physicians regarding anticoagulation for atrial fibrillation: a systematic review. Age Ageing. 2011;40(6):675-683. doi:10.1093/ageing/afr097

Mitchell A, Elmasry Y, van Poelgeest E, Welsh TJ. Anticoagulant use in older persons at risk for falls: therapeutic dilemmas-a clinical review. Eur Geriatr Med. 2023;14(4):683-696. doi:10.1007/s41999-023-00811-z

López-López JA, Sterne JAC, Thom HHZ, et al. Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis. BMJ. 2017;359:j5058. Published 2017 Nov 28. doi:10.1136/bmj.j5058

Müller KE, Blomberg B, Tellevik MG, Jensenius M, Fladeby C, Lier T, et al. Falls in ED patients;do elderly patients on direct oral anticoagulants bleed less than those on Vitamin K antagonist? Scand J Trauma Resusc Emerg Med. 2021;141(3):1–9.

Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543-603. doi:10.1093/eurheartj/ehz405

Ortel TL, Neumann I, Ageno W, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv. 2020;4(19):4693-4738. doi:10.1182/bloodadvances.2020001830

By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372

Purnell JQ. Definitions, Classification, and Epidemiology of Obesity. Endotext [Internet]. 2023 May 4 [cited 2025 Aug 29]; Available from: https://www.ncbi.nlm.nih.gov/books/NBK279167/

Finkelstein EA, Khavjou OA, Thompson H, et al. Obesity and severe obesity forecasts through 2030. Am J Prev Med. 2012;42(6):563-570. doi:10.1016/j.amepre.2011.10.026

Hotoleanu C. Association between obesity and venous thromboembolism. Med Pharm Rep. 2020 Apr;93(2):162-168. doi: 10.15386/mpr-1372. Epub 2020 Apr 22. PMID: 32478322; PMCID: PMC7243888.

Wendelboe AM, Raskob GE. Global Burden of Thrombosis: Epidemiologic Aspects. Circ Res. 2016;118(9):1340-1347. doi:10.1161/CIRCRESAHA.115.306841

Morrish GA, Pai MP, Green B. The effects of obesity on drug pharmacokinetics in humans. Expert Opin Drug Metab Toxicol. 2011;7(6):697-706. doi:10.1517/17425255.2011.570331

Sebaaly J, Kelley D. Direct Oral Anticoagulants in Obesity: An Updated Literature Review. Ann Pharmacother. 2020;54(11):1144-1158. doi:10.1177/1060028020923584

Wallace JL, Reaves AB, Tolley EA, et al. Comparison of initial warfarin response in obese patients versus non-obese patients. J Thromb Thrombolysis. 2013;36(1):96-101. doi:10.1007/s11239-012-0811-x

Barakat AF, Jain S, Masri A, et al. Outcomes of Direct Oral Anticoagulants in Atrial Fibrillation Patients Across Different Body Mass Index Categories. JACC Clin Electrophysiol. 2021;7(5):649-658. doi:10.1016/j.jacep.2021.02.002

Martin KA, Lancki N, Li C, et al. DOAC compared with warfarin for VTE in patients with obesity: a retrospective cohort study conducted through the VENUS network. J Thromb Thrombolysis. 2023;55(4):685-690. doi:10.1007/s11239-023-02774-1

Martin KA, Beyer-Westendorf J, Davidson BL, Huisman MV, Sandset PM, Moll S. Use of direct oral anticoagulants in patients with obesity for treatment and prevention of venous thromboembolism: Updated communication from the ISTH SSC Subcommittee on Control of Anticoagulation. J Thromb Haemost. 2021;19(8):1874-1882. doi:10.1111/jth.15358

Lisman T, Bernal W, Adelmeijer J, Kamphuisen PW, Bos S, Porte RJ. Clinically relevant increases in the international normalized ratio and model of end-stage liver disease score by therapeutic doses of direct oral anticoagulants in patients with cirrhosis. Res Pract Thromb Haemost. 2023;7(1):100052. Published 2023 Jan 14. doi:10.1016/j.rpth.2023.100052

Gatt A, Chen D, Pruthi RK, et al. From vitamin K antagonists to liver international normalized ratio: a historical journey and critical perspective. Semin Thromb Hemost. 2014;40(8):845-851. doi:10.1055/s-0034-1395160

Intagliata NM, Henry ZH, Maitland H, et al. Direct Oral Anticoagulants in Cirrhosis Patients Pose Similar Risks of Bleeding When Compared to Traditional Anticoagulation. Dig Dis Sci. 2016;61(6):1721-1727. doi:10.1007/s10620-015-4012-2

Pereira Portela C, Gautier LA, Zermatten MG, et al. Direct oral anticoagulants in cirrhosis: Rationale and current evidence. JHEP Rep. 2024;6(8):101116. Published 2024 May 9. doi:10.1016/j.jhepr.2024.101116

.

Graff J, Harder S. Anticoagulant therapy with the oral direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban and the thrombin inhibitor dabigatran etexilate in patients with hepatic impairment. Clin Pharmacokinet. 2013;52(4):243-254. doi:10.1007/s40262-013-0034-0

Chen A, Stecker E, A Warden B. Direct Oral Anticoagulant Use: A Practical Guide to Common Clinical Challenges. J Am Heart Assoc. 2020;9(13):e017559. doi:10.1161/JAHA.120.017559

Stangier J, Stähle H, Rathgen K, Roth W, Shakeri-Nejad K. Pharmacokinetics and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor, are not affected by moderate hepatic impairment. J Clin Pharmacol. 2008;48(12):1411-1419. doi:10.1177/0091270008324179

Kubitza D, Roth A, Becka M, et al. Effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of a single dose of rivaroxaban, an oral, direct Factor Xa inhibitor. Br J Clin Pharmacol. 2013;76(1):89-98. doi:10.1111/bcp.12054

Mendell J, Johnson L, Chen S. An open-label, phase 1 study to evaluate the effects of hepatic impairment on edoxaban pharmacokinetics and pharmacodynamics. J Clin Pharmacol. 2015;55(12):1395-1405. doi:10.1002/jcph.550

Blech S, Ebner T, Ludwig-Schwellinger E, Stangier J, Roth W. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos. 2008;36(2):386-399. doi:10.1124/dmd.107.019083.

Steffel J, Collins R, Antz M, et al. 2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation. Europace. 2021;23(10):1612-1676. doi:10.1093/europace/euab065

İndir

Yayınlanan

27 Kasım 2025

Lisans

Lisans