Atriyal fibrilasyonu (AF) olan hastalarda tromboembolik olay riskini azaltmak için oral antikoagülanların rolü çok önemlidir. Bu amaçla, yaygın olarak kullanılan antikoagülan ilaç bir K vitamini antagonisti [vitamin K antagonist (VKA)] olan varfarindir. Fakat nonvalvüler AF'li hastalarda, diğer ilaçlarla minimum düzeyde etkileşime girmesi, gıda ile etkileşimlerinin olmaması ve antikoagülan aktivitelerinin sık izlem gerektirmemesi gibi özellikleri, direkt oral antikoagülanları (DOAK) etkinliği ve güvenliği açısından ön plana çıkarmıştır. Son yıllarda klinik çalışmalardan ve gerçek yaşam kanıtlarından veriler elde edildikçe, DOAK'lerin kullanım endikasyonları artmakta ve birçok bağlamda güvenli ve etkili bir terapötik yaklaşım olarak VKA tedavisinin yerini almaktadır. Çalışmalardan elde edilen kapsamlı sonuçlara göre DOAK'ler VKA'ya kıyasla inme, sistemik emboli ve intrakraniyal kanama vakalarında önemli bir azalma sağlamıştır. DOAK'lerin VKA tedavisine göre bazı avantajları olmasına rağmen etkinlik ve güvenliği sağlamak için tedavide DOAK'ler ve VKA arasındaki tercih aşamasında dikkatli bir karar verme süreci gerekmektedir. AF'si olan ve aynı zamanda farklı komorbiditelere sahip riskli hastalarda DOAK'lerin kullanımıyla ilgili olarak net veriler bulunmamaktadır. Bu derlemede, AF'si olan, perkütan koroner girişim uygulanan, yaşlı, obez, kronik böbrek yetersizliği, karaciğer yetersizliği, siroz hastalığı, kırık riski ve kalp kapak hastalığı olan hastalarda DOAK'lerin kullanımına dair sistematik derleme ve metaanalizlerin sonuçları sunulmuştur. Sonuç olarak, AF'li hastalarda belirtilen komorbidite durumlarında DOAK'leri VKA'ya karşın ön plana çıkaran kanıtlar mevcut olsa da daha fazla çalışmaya ve güçlü kanıtlara ihtiyaç duyulduğu belirtilmektedir.
Anahtar Kelimeler: Atriyal fibrilasyon; iskemik inme; antikoagülanlar; kanama
The role of oral anticoagulants is significant in reducing the risk of thromboembolic events in patients with atrial fibrillation (AF). The anticoagulant drug commonly used for this purpose is warfarin, a vitamin K antagonist (VKA). However, in patients with nonvalvular AF, direct oral anticoagulants (DOAC) have come to the forefront regarding their efficacy and safety due to their minimal interaction with other drugs, no interactions with food, and the fact that their anticoagulant activities do not require frequent monitoring. In recent years, as data from clinical trials and real-life evidence become available, indications for the use of DOACs have increased and are replacing VKA therapy as a safe and effective therapeutic approach in many contexts. Comprehensive results from the studies showed that DOACs significantly reduced stroke, systemic embolism, and intracranial hemorrhage compared to VKA. Although DOACs have some advantages over VKA treatment, careful decision-making is required to choose between DOACs and VKAs in treatment to ensure efficacy and safety. There are no clear data on the use of DOACs in risky patients with AF and different comorbidities. In this review, systematic reviews and meta-analyses on DOACs in patients with AF undergoing percutaneous coronary intervention, elderly, obese, chronic renal failure, liver failure, cirrhosis, fracture risk, and valvular heart disease are presented. In conclusion, although there is evidence that favors DOACs over VKA in the comorbidities stated in patients with AF, it is stated that more studies and strong evidence are needed.
Keywords: Atrial fibrillation; ischemic stroke; anticoagulants; hemorrhage
- January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC Jr, 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(1):104-32. Erratum in: J Am Coll Cardiol. 2019;74(4):599. [PubMed]
- Menke J, Lüthje L, Kastrup A, Larsen J. Thromboembolism in atrial fibrillation. Am J Cardiol. 2010;105(4):502-10. [Crossref] [PubMed]
- Caturano A, Galiero R, Pafundi PC. Atrial Fibrillation and Stroke. A Review on the Use of Vitamin K Antagonists and Novel Oral Anticoagulants. Medicina (Kaunas). 2019;55(10):617. [Crossref] [PubMed] [PMC]
- Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146(12):857-67. [Crossref] [PubMed]
- Owens RE, Kabra R, Oliphant CS. Direct oral anticoagulant use in nonvalvular atrial fibrillation with valvular heart disease: a systematic review. Clin Cardiol. 2017;40(6):407-12. [Crossref] [PubMed] [PMC]
- Farmakis D, Davlouros P, Giamouzis G, Giannakoulas G, Pipilis A, Tsivgoulis G, et al. Direct oral anticoagulants in nonvalvular atrial fibrillation: practical considerations on the choice of agent and dosing. Cardiology. 2018;140(2):126-32. [Crossref] [PubMed]
- 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. [Crossref] [PubMed] [PMC]
- Lip GYH, Banerjee A, Boriani G, Chiang CE, Fargo R, Freedman B, et al. Antithrombotic therapy for atrial fibrillation: CHEST guideline and expert panel report. Chest. 2018;154(5):1121-201. [Crossref] [PubMed]
- Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, 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):955-62. [Crossref] [PubMed]
- Russo V, Bianchi V, Cavallaro C, Vecchione F, De Vivo S, Santangelo L, et al. Efficacy and safety of dabigatran in a "real-life" population at high thromboembolic and hemorrhagic risk: data from MonaldiCare registry. Eur Rev Med Pharmacol Sci. 2015;19(20):3961-7. [PubMed]
- Russo V, Attena E, Mazzone C, Melillo E, Rago A, Galasso G, et al. Real-life performance of edoxaban in elderly patients with atrial fibrillation: a multicenter propensity score-matched cohort study. Clin Ther. 2019;41(8):1598-604. [Crossref] [PubMed]
- Lip GY, Hart RG, Conway DS. Antithrombotic therapy for atrial fibrillation. BMJ. 2002;325(7371):1022-5. [Crossref] [PubMed] [PMC]
- Di Biase L. Use of direct oral anticoagulants in patients with atrial fibrillation and valvular heart lesions. J Am Heart Assoc. 2016;5(2):e002776. [Crossref] [PubMed] [PMC]
- Kimachi M, Furukawa TA, Kimachi K, Goto Y, Fukuma S, Fukuhara S. 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(11):CD011373. [Crossref] [PubMed] [PMC]
- Reers S, Karanatsios G, Borowski M, Kellner M, Reppel M, Waltenberger J. Frequency of atrial thrombus formation in patients with atrial fibrillation under treatment with non-vitamin K oral anticoagulants in comparison to vitamin K antagonists: a systematic review and meta-analysis. Eur J Med Res. 2018;23(1):49. [Crossref] [PubMed] [PMC]
- Bertaglia E, Anselmino M, Zorzi A, Russo V, Toso E, Peruzza F, et al. NOACs and atrial fibrillation: Incidence and predictors of left atrial thrombus in the real world. Int J Cardiol. 2017;249:179-83. [Crossref] [PubMed]
- Raunsø J, Selmer C, Olesen JB, Charlot MG, Olsen AM, Bretler DM, et al. Increased short-term risk of thrombo-embolism or death after interruption of warfarin treatment in patients with atrial fibrillation. Eur Heart J. 2012;33(15):1886-92. [Crossref] [PubMed]
- Sjögren V, Grzymala-Lubanski B, Renlund H, Friberg L, Lip GY, Svensson PJ, et al. Safety and efficacy of well managed warfarin. A report from the Swedish quality register Auricula. Thromb Haemost. 2015;113(6):1370-7. [Crossref] [PubMed]
- Heeringa J, van der Kuip DA, Hofman A, Kors JA, van Herpen G, Stricker BH, et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J. 2006;27(8):949-53. [Crossref] [PubMed]
- Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010;137(2):263-72. [Crossref] [PubMed]
- Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093-100. [Crossref] [PubMed]
- Malik AH, Yandrapalli S, Aronow WS, Panza JA, Cooper HA. Meta-analysis of direct-acting oral anticoagulants compared with warfarin in patients >75 years of age. Am J Cardiol. 2019;123(12):2051-7. [Crossref] [PubMed]
- Caldeira D, Nunes-Ferreira A, Rodrigues R, Vicente E, Pinto FJ, Ferreira JJ. Non-vitamin K antagonist oral anticoagulants in elderly patients with atrial fibrillation: A systematic review with meta-analysis and trial sequential analysis. Arch Gerontol Geriatr. 2019;81:209-214. Erratum in: Arch Gerontol Geriatr. 2019;83:338. [Crossref] [PubMed]
- Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al; ESC Scientific Document Group. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019;40(2):87-165. Erratum in: Eur Heart J. 2019;40(37):3096. [Crossref] [PubMed]
- Gwyn JCV, Thomas MR, Kirchhof P. Triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention: a viewpoint. Eur Heart J Cardiovasc Pharmacother. 2017;3(3):157-62. [Crossref] [PubMed]
- Dewilde WJ, Oirbans T, Verheugt FW, Kelder JC, De Smet BJ, Herrman JP, et al; WOEST study investigators. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381(9872):1107-15. [Crossref] [PubMed]
- Vranckx P, Valgimigli M, Eckardt L, Tijssen J, Lewalter T, Gargiulo G, et al. Edoxaban-based versus vitamin K antagonist-based antithrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised, open-label, phase 3b trial. Lancet. 2019;394(10206):1335-43. [Crossref] [PubMed]
- Gibson CM, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med. 2016;375(25):2423-34. [Crossref] [PubMed]
- Lopes RD, Heizer G, Aronson R, Vora AN, Massaro T, Mehran R, et al; AUGUSTUS Investigators. Antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation. N Engl J Med. 2019;380(16):1509-24. [Crossref] [PubMed]
- Cannon CP, Bhatt DL, Oldgren J, Lip GYH, Ellis SG, Kimura T, Maeng M, Merkely B, Zeymer U, Gropper S, Nordaby M, Kleine E, Harper R, Manassie J, Januzzi JL, Ten Berg JM, Steg PG, Hohnloser SH; RE-DUAL PCI steering committee and investigators. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med. 2017;377(16):1513-24. [Crossref] [PubMed]
- Khan SU, Osman M, Khan MU, Khan MS, Zhao D, Mamas MA, et al. Dual versus triple therapy for atrial fibrillation after percutaneous coronary intervention: a systematic review and meta-analysis. Ann Intern Med. 2020;172(7):474-83. [Crossref] [PubMed] [PMC]
- De Rosa S, Sabatino J, Polimeni A, Sorrentino S, Indolfi C. Dual anti-thrombotic treatment with direct anticoagulants improves clinical outcomes in patients with Atrial Fibrillation with ACS or undergoing PCI. A systematic review and meta-analysis. PLoS One. 2020;15(7):e0235511. [Crossref] [PubMed] [PMC]
- Fauchier L, Philippart R, Clementy N, Bourguignon T, Angoulvant D, Ivanes F, et al. How to define valvular atrial fibrillation? Arch Cardiovasc Dis. 2015;108(10):530-9. [Crossref] [PubMed]
- De Caterina R, Camm AJ. What is "valvular" atrial fibrillation? A reappraisal. Eur. Heart J. 2014;35(47):3328-35. [Crossref] [PubMed]
- Tang LL, Liang SW, Shi HL, Ye JJ. Comparison of outcomes of direct-acting oral anticoagulants vs. vitamin K antagonists in patients with bioprosthetic heart valves or valve repair: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci. 2021;25(15):5006-17. [PubMed]
- Kumar S, Lim E, Covic A, Verhamme P, Gale CP, Camm AJ, et al. Anticoagulation in concomitant chronic kidney disease and atrial fibrillation: JACC review topic of the week. J Am Coll Cardiol. 2019;74(17):2204-15. [Crossref] [PubMed]
- Chokesuwattanaskul R, Thongprayoon C, Tanawuttiwat T, Kaewput W, Pachariyanon P, Cheungpasitporn W. Safety and efficacy of apixaban versus warfarin in patients with end-stage renal disease: Meta-analysis. Pacing Clin Electrophysiol. 2018;41(6):627-34. Erratum in: Pacing Clin Electrophysiol. 2018;41(7):879. [Crossref] [PubMed]
- Siontis KC, Zhang X, Eckard A, Bhave N, Schaubel DE, He K, et al. Outcomes associated with apixaban use in patients with end-stage kidney disease and atrial fibrillation in the united states. Circulation. 2018;138(15):1519-29. Erratum in: Circulation. 2018;138(15):e425. [Crossref] [PubMed] [PMC]
- Coleman CI, Kreutz R, Sood NA, Bunz TJ, Eriksson D, Meinecke AK, et al. Rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and severe kidney disease or undergoing hemodialysis. Am J Med. 2019;132(9):1078-83. [Crossref] [PubMed]
- Lisman T, Caldwell SH, Burroughs AK, Northup PG, Senzolo M, Stravitz RT, et al; Coagulation in Liver Disease Study Group. Hemostasis and thrombosis in patients with liver disease: the ups and downs. J Hepatol. 2010;53(2):362-71. [Crossref] [PubMed]
- Dhar A, Mullish BH, Thursz MR. Anticoagulation in chronic liver disease. J Hepatol. 2017;66(6):1313-26. [Crossref] [PubMed]
- Huang ZC, Li CQ, Liu XY, Cao ZC, Jia HY, Dong Y, et al. Efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation and liver disease: a meta-analysis and systematic review. Cardiovasc Drugs Ther. 2021;35(6):1205-15. [Crossref] [PubMed]
- Hoolwerf EW, Kraaijpoel N, Büller HR, van Es N. Direct oral anticoagulants in patients with liver cirrhosis: A systematic review. Thromb Res. 2018;170:102-8. [Crossref] [PubMed]
- Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981-92. [PubMed]
- López-López JA, Sterne JAC, Thom HHZ, Higgins JPT, Hingorani AD, Okoli GN, et al. Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis. BMJ. 2017;359:j5058. Erratum in: BMJ. 2017;359:j5631. Erratum in: BMJ. 2018;361:k2295. [PubMed] [PMC]
- Kido K, Ngorsuraches S. Comparing the efficacy and safety of direct oral anticoagulants with warfarin in the morbidly obese population with atrial fibrillation. Ann Pharmacother. 2019;53(2):165-70. [Crossref] [PubMed]
- Martin K, Beyer-Westendorf J, Davidson BL, Huisman MV, Sandset PM, Moll S. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost. 2016;14(6):1308-13. [Crossref] [PubMed] [PMC]
- Lavie CJ, Pandey A, Lau DH, Alpert MA, Sanders P. Obesity and atrial fibrillation prevalence, pathogenesis, and prognosis: effects of weight loss and exercise. J Am Coll Cardiol. 2017;70(16):2022-35. [Crossref] [PubMed]
- Proietti M, Guiducci E, Cheli P, Lip GY. Is there an obesity paradox for outcomes in atrial fibrillation? a systematic review and meta-analysis of non-vitamin k antagonist oral anticoagulant trials. Stroke. 2017;48(4):857-66. [Crossref] [PubMed]
- Zhou Y, Ma J, Zhu W. Efficacy and safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation across BMI categories: a systematic review and meta-analysis. Am J Cardiovasc Drugs. 2020;20(1):51-60. [Crossref] [PubMed]
- Thangjui S, Kewcharoen J, Yodsuwan R, Trongtorsak A, Thyagaturu H, Shrestha B, et al. Efficacy and safety of direct oral anticoagulant in morbidly obese patients with atrial fibrillation: systematic review and meta-analysis. Eur Heart J Cardiovasc Pharmacother. 2022;8(4):325-35. [Crossref] [PubMed]
- Yaegashi Y, Onoda T, Tanno K, Kuribayashi T, Sakata K, Orimo H. Association of hip fracture incidence and intake of calcium, magnesium, vitamin D, and vitamin K. Eur J Epidemiol. 2008;23(3):219-25. [Crossref] [PubMed]
- Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ. Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2006;166(12):1256-61. Erratum in: JAMA Intern Med. 2018;178(6):875-6. [Crossref] [PubMed]
- Suttie JW. Warfarin and the biology of the vitamin K dependent proteins. In: Wessler S, Becker CG, Nemerson Y, eds. The New Dimensions of Warfarin Prophylaxis. 1st ed. New York: Springer Science & Business Media; 1987. p.3-16.
- Azuma K, Shiba S, Hasegawa T, Ikeda K, Urano T, Horie-Inoue K, et al. Osteoblast-specific γ-glutamyl carboxylase-deficient mice display enhanced bone formation with aberrant mineralization. J Bone Miner Res. 2015;30(7):1245-54. [Crossref] [PubMed]
- Haffa A, Krueger D, Bruner J, Engelke J, Gundberg C, Akhter M, et al. Diet- or warfarin-induced vitamin K insufficiency elevates circulating undercarboxylated osteocalcin without altering skeletal status in growing female rats. J Bone Miner Res. 2000;15(5):872-8. [Crossref] [PubMed]
- Gu ZC, Zhou LY, Shen L, Zhang C, Pu J, Lin HW, et al. Non-vitamin K antagonist oral anticoagulants vs. Warfarin at risk of fractures: a systematic review and meta-analysis of randomized controlled trials. Front Pharmacol. 2018;9:348. [Crossref] [PubMed] [PMC]
- Norby FL, Bengtson LGS, Lutsey PL, Chen LY, MacLehose RF, Chamberlain AM, et al. Comparative effectiveness of rivaroxaban versus warfarin or dabigatran for the treatment of patients with non-valvular atrial fibrillation. BMC Cardiovasc Disord. 2017;17(1):238. [Crossref] [PubMed] [PMC]
- Wu X, Hu L, Liu J, Gu Q. Association of direct oral anticoagulants vs. Vitamin K antagonists with fractures in atrial fibrillation patients: a systematic review and meta-analysis. Front Cardiovasc Med. 2021;8:713187. [Crossref] [PubMed] [PMC]
.: Process List