Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study
Yıl: 2021 Cilt: 25 Sayı: 3 Sayfa Aralığı: 196 - 204 Metin Dili: İngilizce DOI: 10.5152/AnatolJCardiol.2021.57635 İndeks Tarihi: 23-05-2022
Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study
Öz: Objective: This study aimed to evaluate the safety of direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (NVAF) during daily clinical practice. Methods: This was a prospective study conducted between January 01, 2016, and April 01, 2017, in patients aged ≥18 years with a diagnosis of NVAF. We performed the study in 9 clinical centers from different regions of Turkey, and the mean follow-up period was 12+2 months. We investigated major and minor bleeding events of DOAC. Results: A total of 1807 patients with NVAF were enrolled. The mean age of the patients was 73.6±10.2 years, CHA2DS2-VASc score was 3.6±1.4, and HAS-BLED score was 2±1.2. The most frequently prescribed DOAC was dabigatran 110 mg bid in 409 (22.6%) patients. The patients on apixaban 2.5 mg bid were older (p<0.001). Patients on rivaroxaban 15 mg od also had a higher prevalence of chronic renal failure, 46 (16.7%) patients. A total of 205 (11.4%) bleeding events were observed; among these, 34 (1.9%) patients had major bleeding and 171 (9.4%) patients had minor bleeding. The major and minor bleeding events were 2/273 (0.7%) and 30/273 (10.9%) in patients receiving dabigatran 150 mg bid, 13/409 (3%) and 44/409 (10.7%) in patients receiving dabigatran 110 mg bid, 4/385 (1%) and 42/385 (10.9%) in patients receiving rivaroxaban 20 mg od, 8/276 (2.9%) and 27/276 (9.7%) in patients receiving rivaroxaban 15 mg od, 3/308 (0.9%) and 14/308 (4.5%) in patients receiving apixaban 5 mg bid, 4/156 (2.5%) and 14/156 (9%) in patients receiving apixaban 2.5 mg bid, respectively. The total bleeding events were 17 (5.6%) in patients receiving apixaban 5 mg, less than those receiving other DOACs. On multivariate analyses, rivaroxaban 20 mg od (p=0.002), ATRIA and HAS-BLED scores, and peripheral artery disease were independent indicators of bleeding. The most frequent location of major bleeding was the gastrointestinal system (GIS) [17 (0.9%) patients], and the most frequent location of minor bleeding was the gingiva [45 (2.5%) patients]. Conclusion: This study showed that similar results as the previous real-life study; however, we had some different results, such as the GIS tract bleeding was more frequent in patients receiving dabigatran 110 mg bid. The major and intracranial bleeding events were similar for different DOACs; and among DOACs, only rivaroxaban 20 mg od was associated with a high risk of bleeding.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- 1. Chugh SS, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin EJ, et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation 2014; 129: 837-47. [Crossref]
- 2. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al.; ESC Scientific Document Group. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37: 2893-962. [Crossref]
- 3. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al.; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-51. [Crossref]
- 4. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al.; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-91. [Crossref]
- 5. 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: 981-92. [Crossref]
- 6. Eikelboom J, Merli G. Bleeding with Direct Oral Anticoagulants vs Warfarin: Clinical Experience. Am J Med 2016; 129 (11S): S33-40. [Crossref]
- 7. Nieuwlaat R, Capucci A, Lip GY, Olsson SB, Prins MH, Nieman FH, et al.; Euro Heart Survey Investigators. Antithrombotic treatment in real-life atrial fibrillation patients: a report from the Euro Heart Survey on Atrial Fibrillation. Eur Heart J 2006; 27: 3018-26. [Crossref]
- 8. Altay S, Yıldırımtürk Ö, Çakmak HA, Aşkın L, Sinan ÜY, Beşli F, et al.; NOAC-TURK Study Collaborators. New oral anticoagulants-TURKey (NOAC-TURK): Multicenter cross-sectional study. Anatol J Cardiol 2017; 17: 353-61. [Crossref]
- 9. Başaran Ö, Beton O, Doğan V, Tekinalp M, Aykan AÇ, Kalaycıoğlu E, et al.; RAMSES Study. ReAl-life Multicenter Survey Evaluating Stroke prevention strategies in non-valvular atrial fibrillation (RAMSES study). Anatol J Cardiol 2016; 16: 734-41. [Crossref]
- 10. Ertaş F, Kaya H, Yüksel M, Soydinç MS, Alan S, Ülgen MS. Atrial Fibrillation in Turkey: Epidemiologic Registry (AFTER) study design. Anatol J Cardiol 2013; 13: 339-43. [Crossref]
- 11. Emren SV, Şenöz O, Bilgin M, Beton O, Aslan A, Taşkin U, et al. Drug Adherence in Patients With Nonvalvular Atrial Fibrillation Taking Non-Vitamin K Antagonist Oral Anticoagulants in Turkey: NOAC-TR. Clin Appl Thromb Hemost 2018; 24: 525-31. [Crossref]
- 12. EINSTEIN Investigators, Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363: 2499-510. [Crossref]
- 13. 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: 263-72. [Crossref]
- 14. 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: 1093-100. [Crossref]
- 15. Fang MC, Go AS, Chang Y, Borowsky LH, Pomernacki NK, Udaltsova N, et al. A new risk scheme to predict warfarin-associated hemorrhage: The ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study. J Am Coll Cardiol 2011; 58: 395-401. [Crossref]
- 16. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999; 130: 461-70. [Crossref]
- 17. Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3: 692-4. [Crossref]
- 18. Sørensen R, Gislason G, Torp-Pedersen C, Olesen JB, Fosbøl EL, Hvidtfeldt MW, et al. Dabigatran use in Danish atrial fibrillation patients in 2011: a nationwide study. BMJ Open 2013; 3: e002758.[Crossref]
- 19. 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. [Crossref]
- 20. Königsbrügge O, Simon A, Domanovits H, Pabinger I, Ay C. Thromboembolic events, bleeding, and drug discontinuation in patients with atrial fibrillation on anticoagulation: a prospective hospital-based registry. BMC Cardiovasc Disord 2016; 16: 254. [Crossref]
- 21. Halvorsen S, Ghanima W, Fride Tvete I, Hoxmark C, Falck P, Solli O, et al. A nationwide registry study to compare bleeding rates in patients with atrial fibrillation being prescribed oral anticoagulants. Eur Heart J Cardiovasc Pharmacother 2017; 3: 28-36. [Crossref]
- 22. Lip GY, Laroche C, Dan GA, Santini M, Kalarus Z, Rasmussen LH, et al. A prospective survey in European Society of Cardiology member countries of atrial fibrillation management: baseline results of EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry. Europace 2014; 16: 308-19. [Crossref]
- 23. Helmert S, Marten S, Mizera H, Reitter A, Sahin K, Tittl L, et al. Effectiveness and safety of apixaban therapy in daily-care patients with atrial fibrillation: results from the Dresden NOAC Registry. J Thromb Thrombolysis 2017; 44: 169-78. [Crossref]
- 24. Camm AJ, Amarenco P, Haas S, Hess S, Kirchhof P, Kuhls S, et al.; XANTUS Investigators. XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J 2016; 37: 1145-53. [Crossref]
- 25. Navarro-Almenzar B, Cerezo-Manchado JJ, Caro-Martinez C, García-Candel F, Flores Blanco PJ, Ruiz GE, et al. Real-life behaviour of direct oral anticoagulants in a Spanish cohort with non-valvular atrial fibrillation: Refase Registry. Curr Med Res Opin 2019; 35: 2035-41. [Crossref]
- 26. Blin P, Fauchier L, Dureau-Pournin C, Sacher F, Dallongeville J, Bernard MA, et al. Effectiveness and Safety of Rivaroxaban 15 or 20 mg Versus Vitamin K Antagonists in Nonvalvular Atrial Fibrillation. Stroke 2019; 50: 2469-76. [Crossref]
- 27. Huang HY, Lin SY, Cheng SH, Wang CC. Effectiveness and Safety of Different Rivaroxaban Dosage Regimens in Patients with Non-Valvular Atrial Fibrillation: A Nationwide, Population-Based Cohort Study. Sci Rep 2018; 8: 3451. [Crossref]
- 28. Bahit MC, Lopes RD, Wojdyla DM, Held C, Hanna M, Vinereanu D, et al. Non-major bleeding with apixaban versus warfarin in patients with atrial fibrillation. Heart 2017; 103: 623-8. [Crossref]
- 29. Laine L. Bleeding With Direct Oral Anticoagulants: The Gastrointestinal Tract and Beyond. Clin Gastroenterol Hepatol 2017; 15: 1665-7. [Crossref]
- 30. Ward R, Huang Z, Rockhold FW, Baumgartner I, Berger JS, Blomster JI, et al. Major bleeding in patients with peripheral artery disease: Insights from the EUCLID trial. Am Heart J 2020; 220: 51-8. [Crossref]
- 31. Deitelzweig S, Farmer C, Luo X, Li X, Vo L, Mardekian J, et al. Comparison of major bleeding risk in patients with non-valvular atrial fibrillation receiving direct oral anticoagulants in the real-world setting: a network meta-analysis. Curr Med Res Opin 2018; 34: 487-98. [Crossref]
- 32. Larsen TB, Skjøth F, Nielsen PB, Kjældgaard JN, Lip GY. Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ 2016; 353: i3189. [Crossref]
| APA | Gedikli O, Altay S, Ünlü S, Cakmak H, askin l, Yanik A, Besli F, Sinan U, Canpolat U, ŞAHİN M, Pehlivanoğlu S (2021). Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study. , 196 - 204. 10.5152/AnatolJCardiol.2021.57635 |
| Chicago | Gedikli Omer,Altay Servet,Ünlü Serkan,Cakmak Huseyin Altug,askin lutfu,Yanik Ahmet,Besli Feyzullah,Sinan Umit Yasar,Canpolat Ugur,ŞAHİN Mahmut,Pehlivanoğlu Seçkin Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study. (2021): 196 - 204. 10.5152/AnatolJCardiol.2021.57635 |
| MLA | Gedikli Omer,Altay Servet,Ünlü Serkan,Cakmak Huseyin Altug,askin lutfu,Yanik Ahmet,Besli Feyzullah,Sinan Umit Yasar,Canpolat Ugur,ŞAHİN Mahmut,Pehlivanoğlu Seçkin Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study. , 2021, ss.196 - 204. 10.5152/AnatolJCardiol.2021.57635 |
| AMA | Gedikli O,Altay S,Ünlü S,Cakmak H,askin l,Yanik A,Besli F,Sinan U,Canpolat U,ŞAHİN M,Pehlivanoğlu S Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study. . 2021; 196 - 204. 10.5152/AnatolJCardiol.2021.57635 |
| Vancouver | Gedikli O,Altay S,Ünlü S,Cakmak H,askin l,Yanik A,Besli F,Sinan U,Canpolat U,ŞAHİN M,Pehlivanoğlu S Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study. . 2021; 196 - 204. 10.5152/AnatolJCardiol.2021.57635 |
| IEEE | Gedikli O,Altay S,Ünlü S,Cakmak H,askin l,Yanik A,Besli F,Sinan U,Canpolat U,ŞAHİN M,Pehlivanoğlu S "Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study." , ss.196 - 204, 2021. 10.5152/AnatolJCardiol.2021.57635 |
| ISNAD | Gedikli, Omer vd. "Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study". (2021), 196-204. https://doi.org/10.5152/AnatolJCardiol.2021.57635 |
| APA | Gedikli O, Altay S, Ünlü S, Cakmak H, askin l, Yanik A, Besli F, Sinan U, Canpolat U, ŞAHİN M, Pehlivanoğlu S (2021). Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study. The Anatolian Journal of Cardiology, 25(3), 196 - 204. 10.5152/AnatolJCardiol.2021.57635 |
| Chicago | Gedikli Omer,Altay Servet,Ünlü Serkan,Cakmak Huseyin Altug,askin lutfu,Yanik Ahmet,Besli Feyzullah,Sinan Umit Yasar,Canpolat Ugur,ŞAHİN Mahmut,Pehlivanoğlu Seçkin Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study. The Anatolian Journal of Cardiology 25, no.3 (2021): 196 - 204. 10.5152/AnatolJCardiol.2021.57635 |
| MLA | Gedikli Omer,Altay Servet,Ünlü Serkan,Cakmak Huseyin Altug,askin lutfu,Yanik Ahmet,Besli Feyzullah,Sinan Umit Yasar,Canpolat Ugur,ŞAHİN Mahmut,Pehlivanoğlu Seçkin Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study. The Anatolian Journal of Cardiology, vol.25, no.3, 2021, ss.196 - 204. 10.5152/AnatolJCardiol.2021.57635 |
| AMA | Gedikli O,Altay S,Ünlü S,Cakmak H,askin l,Yanik A,Besli F,Sinan U,Canpolat U,ŞAHİN M,Pehlivanoğlu S Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study. The Anatolian Journal of Cardiology. 2021; 25(3): 196 - 204. 10.5152/AnatolJCardiol.2021.57635 |
| Vancouver | Gedikli O,Altay S,Ünlü S,Cakmak H,askin l,Yanik A,Besli F,Sinan U,Canpolat U,ŞAHİN M,Pehlivanoğlu S Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study. The Anatolian Journal of Cardiology. 2021; 25(3): 196 - 204. 10.5152/AnatolJCardiol.2021.57635 |
| IEEE | Gedikli O,Altay S,Ünlü S,Cakmak H,askin l,Yanik A,Besli F,Sinan U,Canpolat U,ŞAHİN M,Pehlivanoğlu S "Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study." The Anatolian Journal of Cardiology, 25, ss.196 - 204, 2021. 10.5152/AnatolJCardiol.2021.57635 |
| ISNAD | Gedikli, Omer vd. "Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study". The Anatolian Journal of Cardiology 25/3 (2021), 196-204. https://doi.org/10.5152/AnatolJCardiol.2021.57635 |
