Risk of Bleeding With 2 Doses of Dabigatran Compared With Warfarin in Older and Younger Patients With Atrial Fibrillation: An Analysis of the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) Trial
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BACKGROUND: Dabigatran 150 and 110 mg twice a day and warfarin are effective for stroke prevention in atrial fibrillation. The purpose of this study was to compare their risks of bleeding in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial. METHODS AND RESULTS: The RE-LY trial randomized 18 113 patients to receive dabigatran 110 or 150 mg twice a day or warfarin dose adjusted to an international normalized ratio of 2.0 to 3.0 for a median follow-up of 2.0 years. Compared with warfarin, dabigatran 110 mg twice a day was associated with a lower risk of major bleeding (2.87% versus 3.57%; P=0.002), whereas dabigatran 150 mg twice a day was associated with a similar risk of major bleeding (3.31% versus 3.57%; P=0.32). There was a significant treatment-by-age interaction, such that dabigatran 110 mg twice a day compared with warfarin was associated with a lower risk of major bleeding in patients aged <75 years (1.89% versus 3.04%; P<0.001) and a similar risk in those aged ≥75 years (4.43% versus 4.37%; P=0.89; P for interaction <0.001), whereas dabigatran 150 mg twice a day compared with warfarin was associated with a lower risk of major bleeding in those aged <75 years (2.12% versus 3.04%; P<0.001) and a trend toward higher risk of major bleeding in those aged ≥75 years (5.10% versus 4.37%; P=0.07; P for interaction <0.001). The interaction with age was evident for extracranial bleeding, but not for intracranial bleeding, with the risk of the latter being consistently reduced with dabigatran compared with warfarin irrespective of age. CONCLUSIONS: In patients with atrial fibrillation at risk for stroke, both doses of dabigatran compared with warfarin have lower risks of both intracranial and extracranial bleeding in patients aged <75 years. In those aged ≥75 years, intracranial bleeding risk is lower but extracranial bleeding risk is similar or higher with both doses of dabigatran compared with warfarin. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.
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The risk of gastrointestinal bleeds was comparable to warfarin on dabigatran 110 mg twice daily and on apixaban 5 mg twice daily.
“The risk of gastrointestinal bleeds was comparable to warfarin on dabigatran 110 mg twice daily 490 and on apixaban 5 mg twice daily 319”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [490]
Compared with warfarin, the risk of gastrointestinal bleeds was increased for dabigatran 150 mg twice daily, rivaroxaban 20 mg once daily, and edoxaban 60 mg once daily.
“Compared with warfarin, the risk of gastrointestinal bleeds was increased for dabigatran 150 mg twice daily, 396, 490 rivaroxaban 20 mg once daily, 491 and edoxaban 60 mg once daily.321”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [490]
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Cites
Dabigatran versus warfarin in patients with atrial fibrillation
Connolly, S. J., Ezekowitz, M. D., Yusuf, S., Eikelboom, J., Oldgren, J., Parekh, A., Pogue, J., Reilly, P. A., Themeles, E., Varrone, J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0905561 · Cited by 11,215 · see citing works
Wallentin, L. C., Yusuf, S., Ezekowitz, M. D., Alings, M., Flather, M. D., Franzosi, M. G., Pais, P. S., Dans, A., Eikelboom, J. W., Oldgren, J., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)61194-4 · Cited by 1,011 · see citing works
Oates, J. A., Wood, A. J. J., & Hirsh, J. (1991) · New England Journal of Medicine · doi:10.1056/nejm199106273242606 · Cited by 561 · see citing works
Eriksson, B. I., Quinlan, D. J., & Weitz, J. I. (2008) · Clinical Pharmacokinetics · doi:10.2165/0003088-200948010-00001 · Cited by 519 · see citing works
Tissue Factor in Cardiovascular Diseases: Molecular Mechanisms and Clinical Implications
Steffel, J., Lüscher, T. F., & Tanner, F. C. (2006) · Circulation · doi:10.1161/circulationaha.105.567297 · Cited by 456 · see citing works
Fleck, R. A., Rao, L. V. M., Rapaport, S. I., & Varki, N. M. (1990) · Thrombosis Research · doi:10.1016/0049-3848(90)90148-6 · Cited by 361 · see citing works
The Role of Tissue Factor and Factor VIIa in Hemostasis
Mackman, N. (2009) · Anesthesia & Analgesia · doi:10.1213/ane.0b013e31819bceb1 · Cited by 338 · see citing works
Ezekowitz, M. D., Connolly, S. J., Parekh, A., Reilly, P. A., Varrone, J., Wang, S., Oldgren, J., Themeles, E., Wallentin, L. C., & Yusuf, S. (2009) · American Heart Journal · doi:10.1016/j.ahj.2009.02.005 · Cited by 332 · see citing works
Lower GI Bleeding: Epidemiology and Diagnosis
Strate, L. L. (2005) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2005.08.007 · Cited by 281 · see citing works
Bleeding During Warfarin and Aspirin Therapy in Patients With Atrial Fibrillation
Gulløv, A. L., Koefoed, B. G., & Petersen, P. (1999) · Archives of Internal Medicine · doi:10.1001/archinte.159.12.1322 · Cited by 229 · see citing works
Sjöblom, L., Hårdemark, H., Lindgren, A., Norrving, B. G., Fahlén, M., Samuelsson, M., Stigendal, L., Stockelberg, D., Taghavi, A., Wallrup, L., et al. (2001) · Stroke · doi:10.1161/hs1101.098523 · Cited by 228 · see citing works
Warfarin Dosing in Patients With Impaired Kidney Function
Limdi, N. A., Limdi, M. A., Cavallari, L. H., Anderson, A. M., Crowley, M. R., Baird, M. F., Allon, M., & Beasley, T. M. (2010) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2010.05.023 · Cited by 177 · see citing works
Predictors of Outcome in Warfarin-Related Intracerebral Hemorrhage
Zubkov, A. Y., Mandrekar, J. N., Claassen, D. O., Manno, E. M., Wijdicks, E. F. M., & Rabinstein, A. A. (2008) · Archives of Neurology · doi:10.1001/archneur.65.10.1320 · Cited by 127 · see citing works
Combined antiplatelet and anticoagulant therapy: clinical benefits and risks
Eikelboom, J. W., & Hirsh, J. (2007) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2007.02499.x · Cited by 91 · see citing works
Anticoagulant (Fluindione)-Aspirin Combination in Patients with High-Risk Atrial Fibrillation
Lechat, P. P., Lardoux, H., Mallet, A., Sanchez-Peña, P., Dérumeaux, G., Lecompte, T., Maillard, L., Mas, J., Mentré, F., Pousset, F., et al. (2001) · Cerebrovascular Diseases · doi:10.1159/000047711 · Cited by 85 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
2013 ACCF/AHA Guideline for the Management of Heart Failure
Yancy, C. W., Jessup, M., Bozkurt, B., Butler, J., Casey, D. E., Drazner, M. H., Fonarow, G. C., Geraci, S. A., Horwich, T., Januzzi, J. L., et al. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.05.019 · Cited by 12,536 · see citing works
Hindricks, G., Potpara, T., Dagres, N., Arbelo, E., Bax, J. J., Blomström‐Lundqvist, C., Boriani, G., Castella, M., Dan, G.-A., Dilaveris, P., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehaa612 · Cited by 10,225 · see citing works
Apixaban versus warfarin in patients with atrial fibrillation
Granger, C. B., Alexander, J. H., McMurray, J. J. V., Lopes, R. D., Hylek, E. M., Hanna, M., Al-Khalidi, H. R., Ansell, J., Atar, D., Avezum, A., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1107039 · Cited by 8,943 · see citing works
2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation
January, C. T., Wann, L. S., Alpert, J. S., Calkins, H. G., Cigarroa, J. E., Cleveland, J. C., CONTI, J. B., Ellinor, P. T., Ezekowitz, M. D., Field, M. E., et al. (2014) · Circulation · doi:10.1161/cir.0000000000000041 · Cited by 7,119 · see citing works
2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P. F., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castellà, M., Diener, H., Heidbüchel, H., Hendriks, J., et al. (2016) · EP Europace · doi:10.1093/europace/euw295 · Cited by 6,438 · see citing works
2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castella, M., Diener, H.-C., Heidbuchel, H., Hendriks, J., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw210 · Cited by 6,418 · see citing works
Ruff, C. T., Giugliano, R. P., Braunwald, E., Hoffman, E. B., Deenadayalu, N., Ezekowitz, M. D., Camm, A. J., Weitz, J. I., Lewis, B. S., Parkhomenko, A., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(13)62343-0 · Cited by 5,051 · see citing works
2012 focused update of the ESC Guidelines for the management of atrial fibrillation
Authors Task Force Members, Camm, A. J., Lip, G. Y. H., Caterina, R. D., Savelieva, I., Atar, D., Hohnloser, S. H., Hindricks, G., Kirchhof, P. F., Bax, J. J., et al. (2012) · EP Europace · doi:10.1093/europace/eus305 · Cited by 3,814 · see citing works
2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation
January, C. T., Wann, L. S., Alpert, J. S., Calkins, H., Cigarroa, J. E., Cleveland, J. C., Conti, J. B., Ellinor, P. T., Ezekowitz, M. D., Field, M. E., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.03.022 · Cited by 2,955 · see citing works
2012 focused update of the ESC Guidelines for the management of atrial fibrillation
Authors Task Force Members, Camm, A. J., Lip, G. Y. H., Caterina, R. D., Savelieva, I., Atar, D., Hohnloser, S. H., Hindricks, G., Kirchhof, P. F., Bax, J. J., et al. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs253 · Cited by 2,898 · see citing works
Meschia, J. F., Bushnell, C., Boden-Albala, B., Braun, L. T., Bravata, D. M., Chaturvedi, S., Creager, M. A., Eckel, R. H., Elkind, M. S. V., Fornage, M., et al. (2014) · Stroke · doi:10.1161/str.0000000000000046 · Cited by 2,650 · see citing works
Steffel, J., Verhamme, P., Potpara, T. S., Albaladejo, P., Antz, M., Desteghe, L., Haeusler, K. G., Oldgren, J., Reinecke, H., Roldan-Schilling, V., et al. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehy136 · Cited by 2,123 · see citing works
Dabigatran versus warfarin in patients with mechanical heart valves
Eikelboom, J. W., Connolly, S. J., Brueckmann, M., Granger, C. B., Kappetein, A. P., Mack, M. J., Blatchford, J., Devenny, K., Friedman, J., Guiver, K., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1300615 · Cited by 1,506 · see citing works
“Death, stroke, systemic embolism, or myocardial infarction 11 (8) 2 (3) 2 (6) 0 13 (8) 2 (2) 3.”
Influential2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castella, M., Diener, H.-C., Heidbuchel, H., Hendriks, J., et al. (2016) · European Journal of Cardio-Thoracic Surgery · doi:10.1093/ejcts/ezw313 · Cited by 1,403 · see citing works
Steffel, J., Collins, R., Antz, M., Cornu, P., Desteghe, L., Haeusler, K. G., Oldgren, J., Reinecke, H., Roldan-Schilling, V., Rowell, N., et al. (2021) · EP Europace · doi:10.1093/europace/euab065 · Cited by 1,132 · see citing works
Self-citationHeidbüchel, H., Verhamme, P. B., Alings, M., Antz, M., Diener, H., Hacke, W., Oldgren, J., Sinnaeve, P., Camm, A. J., & Kirchhof, P. F. (2015) · EP Europace · doi:10.1093/europace/euv309 · Cited by 1,114 · see citing works
Management of severe perioperative bleeding
Kozek‐Langenecker, S. A., Afshari, A., Albaladejo, P., Aldecoa, C., ROBERTIS, E. D., Filipescu, D. C., Fries, D. R., Görlinger, K., Haas, T., Imberger, G. L., et al. (2013) · European Journal of Anaesthesiology · doi:10.1097/eja.0b013e32835f4d5b · Cited by 900 · see citing works
Reilly, P. A., Lehr, T., Haertter, S., Connolly, S. J., Yusuf, S., Eikelboom, J. W., Ezekowitz, M. D., Nehmiz, G., Wang, S., & Wallentin, L. C. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.07.104 · Cited by 834 · see citing works
Heidbuchel, H., Verhamme, P., Alings, M., Antz, M., Hacke, W., Oldgren, J., Sinnaeve, P., Camm, A. J., & Kirchhof, P. (2013) · Europace · doi:10.1093/europace/eut083 · Cited by 792 · see citing works
Graham, D. J., Reichman, M. E., Wernecke, M., Zhang, R., Southworth, M. R., Levenson, M., Sheu, T.-C., Mott, K., Goulding, M. R., Houstoun, M., et al. (2015) · Circulation · doi:10.1161/circulationaha.114.012061 · Cited by 644 · see citing works
National trends in ambulatory oral anticoagulant use
Barnes, G. D., Lucas, E., Alexander, G. C., & Goldberger, Z. D. (2015) · The American Journal of Medicine · doi:10.1016/j.amjmed.2015.05.044 · Cited by 598 · see citing works
Andrade, J. G., Aguilar, M., Atzema, C. L., Bell, A., Cairns, J. A., Cheung, C. C., Cox, J. L., Dorian, P., Gladstone, D. J., Healey, J. S., et al. (2020) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2020.09.001 · Cited by 568 · see citing works
Skanes, A. C., Healey, J. S., Cairns, J. A., Dorian, P., Gillis, A. M., McMurtry, M. S., Mitchell, L. B., Verma, A., & Nattel, S. (2012) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2012.01.021 · Cited by 494 · see citing works
Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment
Fujimoto, K., Fujishiro, M., Kato, M., Higuchi, K., Iwakiri, R., Sakamoto, C., Uchiyama, S., Kashiwagi, A., Ogawa, H., Murakami, K., et al. (2013) · Digestive Endoscopy · doi:10.1111/den.12183 · Cited by 463 · see citing works
Halperin, J. L., Hankey, G. J., WOJDYLA, D. M., Piccini, J. P., Lokhnygina, Y. V., Patel, M. R., BREITHARDT, G. E., Singer, D. E., Becker, R. C., Hacke, W., et al. (2014) · Circulation · doi:10.1161/circulationaha.113.005008 · Cited by 432 · see citing works
Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation
Calkins, H. G., Willems, S., Gerstenfeld, E. P., Verma, A., SCHILLING, R. J., Hohnloser, S. H., Okumura, K., Serota, H., Nordaby, M., Guiver, K., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1701005 · Cited by 432 · see citing works
Yao, X., Abraham, N. S., Sangaralingham, L. R., Bellolio, F., McBane, R. D., Shah, N. D., & Noseworthy, P. A. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.116.003725 · Cited by 421 · see citing works
“Analyses of RE-LY data suggested a lower risk of major bleeding in patients aged <75 years but a trend toward higher risk in patients aged ≥75 years.(46) Moreover, physicians tended to prescribe medications to patients who were similar Table 4.”
ResultHeidbüchel, H., Verhamme, P. B., Alings, M., Antz, M., Hacke, W., Oldgren, J., Sinnaeve, P., Camm, A. J., & Kirchhof, P. F. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht134 · Cited by 404 · see citing works
Larsen, T. B., Rasmussen, L. H., Skjøth, F., Due, K. M., Callréus, T., Rosenzweig, M., & Lip, G. Y. H. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.03.020 · Cited by 402 · see citing works
Hijazi, Z., Hohnloser, S. H., Oldgren, J., Andersson, U., Connolly, S. J., Eikelboom, J. W., Ezekowitz, M. D., Reilly, P. A., Siegbahn, A., Yusuf, S., et al. (2014) · Circulation · doi:10.1161/circulationaha.113.003628 · Cited by 396 · see citing works
Self-citationCarnicelli, A., Hong, H., Connolly, S. J., Eikelboom, J. W., Giugliano, R. P., Morrow, D. A., Patel, M. R., Wallentin, L. C., Alexander, J. H., Bahit, M. C., et al. (2022) · Circulation · doi:10.1161/circulationaha.121.056355 · Cited by 390 · see citing works
Cardiovascular effects and safety of (non-aspirin) NSAIDs
Schjerning, A.-M., McGettigan, P., & Gislason, G. (2020) · Nature Reviews Cardiology · doi:10.1038/s41569-020-0366-z · Cited by 387 · see citing works
Efficacy and Safety of the Novel Oral Anticoagulants in Atrial Fibrillation
Dentali, F., Riva, N., Crowther, M. A., Turpie, A. G. G., Lip, G. Y. H., & Ageno, W. (2012) · Circulation · doi:10.1161/circulationaha.112.115410 · Cited by 380 · see citing works
Halvorsen, S., Atar, D., Yang, H., Caterina, R. D., Erol, Ç., Garcia, D., Granger, C. B., Hanna, M., Held, C., Husted, S., et al. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu046 · Cited by 371 · see citing works
Abraham, N. S., Singh, S., Alexander, G. C., Heien, H. C., Haas, L. R., Crown, W. H., & Shah, N. D. (2015) · BMJ · doi:10.1136/bmj.h1857 · Cited by 346 · see citing works
Hori, M., Connolly, S. J., Zhu, J., Liu, L., Lau, C., Pais, P. S., Xavier, D., Kim, S. S., Omar, R., Dans, A. L., et al. (2013) · Stroke · doi:10.1161/strokeaha.113.000990 · Cited by 328 · see citing works
“In contrast, we have previously reported that there is an interaction between age and the bleeding effects of both doses of dabigatran compared with warfarin, which indicates that the benefits of dabigatran compared with warfarin seen in younger patients are attenuated significantly in older patients.(6) This age inte…”
ResultBrieger, D. B., Amerena, J. V., Attia, J., Bajorek, B. V., Chan, K. H., Connell, C., Freedman, B., Ferguson, C., Hall, T. L., Haqqani, H. M., et al. (2018) · Heart Lung and Circulation · doi:10.1016/j.hlc.2018.06.1043 · Cited by 328 · see citing works
“Although data from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study suggested dabigatran has acceptable safety and efficacy in the elderly when compared to warfarin [318,319], other cohort studies [320–322] suggest an increased GI bleeding risk.”
EHRA/EAPCI expert consensus statement on catheter-based left atrial appendage occlusion
Meier, B., Blaauw, Y., Khattab, A. A., Lewalter, T., Sievert, H., Tondo, C., Glikson, M., ESC Scientific Document Group, Lip, G. Y. H., López-Mínguez, J. R., et al. (2014) · EP Europace · doi:10.1093/europace/euu174 · Cited by 327 · see citing works
National Trends in Oral Anticoagulant Use in the United States, 2007 to 2011
Kirley, K., Qato, D. M., Kornfield, R., Stafford, R. S., & Alexander, G. C. (2012) · Circulation Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.112.967299 · Cited by 310 · see citing works
“The RE-LY trial reported a lower risk of major bleeding for dabigatran compared with warfarin among individuals <75 years of age, but a nonstatistically significant trend toward an increased risk of major bleeding among those ≥75 years of age.(36) From a clinic perspective, however, dabigatran use in the most elderly…”
BackgroundCarnicelli, A., Hong, H., Connolly, S. J., Eikelboom, J. W., Giugliano, R. P., Morrow, D. A., Patel, M. R., Wallentin, L. C., Alexander, J. H., Bahit, M. C., et al. (2022) · Archive ouverte UNIGE (University of Geneva) · Cited by 304 · see citing works
Kato, E. T., Giugliano, R. P., Ruff, C. T., Koretsune, Y., Yamashita, T., Kiss, R. G., Nordio, F., Murphy, S. A., Kimura, T., Jin, J., et al. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.116.003432 · Cited by 288 · see citing works
“Only the HDER regimen has been approved by regulatory authorities around the world for stroke prevention in patients with AF.”
InfluentialManagement and Outcomes of Major Bleeding During Treatment With Dabigatran or Warfarin
Majeed, A., Hwang, H.-G., Connolly, S. J., Eikelboom, J. W., Ezekowitz, M. D., Wallentin, L. C., Brueckmann, M., Fraessdorf, M., Yusuf, S., & Schulman, S. (2013) · Circulation · doi:10.1161/circulationaha.113.002332 · Cited by 277 · see citing works
“There was no interaction between renal function as assessed by the Cockcroft-Gault formula and treatment, which is a surprising finding because renal function is a determinant of dabigatran exposure.(23) Other analyses have not consistently shown that renal dysfunction is a risk factor for bleeding in patients treated…”
Oral Antithrombotic Agents for the Prevention of Stroke in Nonvalvular Atrial Fibrillation
Furie, K. L., Goldstein, L. B., Albers, G. W., Khatri, P., Neyens, R. R., Turakhia, M. P., Turan, T. N., & Wood, K. (2012) · Stroke · doi:10.1161/str.0b013e318266722a · Cited by 269 · see citing works
“001).(27) The rate of MI was higher with dabigatran 150 mg twice daily (0.”
BackgroundRisk of Bleeding With Dabigatran in Atrial Fibrillation
Hernandez, I., Baik, S. H., Piñera, A., & Zhang, Y. (2014) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2014.5398 · Cited by 263 · see citing works
Guidelines for Pharmacotherapy of Atrial Fibrillation (JCS 2013):– Digest Version –
JCSJointWorkingGroup (2014) · Circulation · Cited by 261 · see citing works
Anticoagulation Drug Therapy: A Review
Harter, K., Levine, M. S., & Henderson, S. O. (2015) · Western Journal of Emergency Medicine · doi:10.5811/westjem.2014.12.22933 · Cited by 259 · see citing works
Genetic Determinants of Dabigatran Plasma Levels and Their Relation to Bleeding
Paré, G., Eriksson, N., Lehr, T., Connolly, S. J., Eikelboom, J. W., Ezekowitz, M. D., Axelsson, T., Haertter, S., Oldgren, J., Reilly, P. A., et al. (2013) · Circulation · doi:10.1161/circulationaha.112.001233 · Cited by 256 · see citing works
“daily) versus higher (150 mg twice daily) dose of dabigatran in the overall study.(16) The observed genetic effect was thus”
BackgroundHow I treat with anticoagulants in 2012: new and old anticoagulants, and when and how to switch
Schulman, S., & Crowther, M. A. (2012) · Blood · doi:10.1182/blood-2011-10-378950 · Cited by 247 · see citing works
Steffel, J., Verhamme, P. B., Potpara, T., Albaladejo, P., Antz, M., Desteghe, L., Hæusler, K. G., Oldgren, J., Reinecke, H., Roldán, V., et al. (2018) · EP Europace · doi:10.1093/europace/euy054 · Cited by 246 · see citing works
Sharma, M., Cornelius, V. R., Patel, J. P., Davies, G., & Molokhia, M. (2015) · Circulation · doi:10.1161/circulationaha.114.013267 · Cited by 241 · see citing works
“The subgroup analysis of the dabigatran phase III, Re-ly study, suggested that major bleeding risk may increase with age for dabigatran.(39) Our study has suggested, however, that this risk increase is not significantly greater than for VKA.”
ResultKirchhof, P. F., Lip, G. Y. H., Gelder, I. C. V., Bax, J. J., Hylek, E. M., Kääb, S., Schotten, U., Wegscheider, K., Boriani, G., Brandes, A., et al. (2011) · EP Europace · doi:10.1093/europace/eur241 · Cited by 242 · see citing works
Andreotti, F., Rocca, B., Husted, S., Ajjan, R., ten Berg, J. M., Cattaneo, M., Collet, J., Caterina, R. D., Fox, K. A. A., Halvorsen, S., et al. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv304 · Cited by 237 · see citing works
“warfarin, irrespective of age and dose.(66) Gastrointestinal bleeds instead were more common with dabigatran 150-mg b.”
BackgroundWever‐Pinzon, O., Selzman, C. H., Drakos, S. G., Saidi, A., Stoddard, G. J., Gilbert, E. M., Labedi, M. R., Reid, B. B., Davis, E. S., Kfoury, A. G., et al. (2013) · Circulation Heart Failure · doi:10.1161/circheartfailure.112.000206 · Cited by 234 · see citing works
Goodman (2014) · doi:10.1016/j.jacc.2013.11.013 · Cited by 228 · see citing works
Assessing bleeding risk in patients taking anticoagulants
Shoeb, M., & Fang, M. C. (2013) · Journal of Thrombosis and Thrombolysis · doi:10.1007/s11239-013-0899-7 · Cited by 228 · see citing works
“In addition, elderly patients and those with renal impairment may be at elevated risk of extracranial bleeding on dabigatran [24].”
Chan, E. W., Lau, W. C. Y., Leung, W. K., Mok, M. T. C., He, Y., Tong, T. S. M., & Wong, I. C. K. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.05.002 · Cited by 227 · see citing works
Pros and cons of new oral anticoagulants
Bauer, K. A. (2013) · Hematology · doi:10.1182/asheducation-2013.1.464 · Cited by 227 · see citing works
2020 Clinical guidelines for Atrial fibrillation and atrial flutter
Arakelyan, M. S., Bockeria, L. A., Vasilieva, E., Sp, G., Golukhova, E. Z., Gorev, M. V., Davtyan, K. V., Drapkina, O. M., Станиславовна, К. Е., Kuchinskaya, Е. А., et al. (2021) · Russian Journal of Cardiology · doi:10.15829/1560-4071-2021-4594 · Cited by 255 · see citing works
Lip, G. Y. H., Diener, H., Brueckmann, M., van Ryn, J., Clemens, A., & Huisman, M. V. (2012) · Thrombosis and Haemostasis · doi:10.1160/th11-10-0718 · Cited by 218 · see citing works
Eikelboom, J. W., Berger, P. B., Holmes, D. R., Bhatt, D. L., Becker, R. C., Angiolill, D., Faxon, D. P., & Moliterno, D. J. (2011) · Thrombosis and Haemostasis · doi:10.1160/th11-04-0262 · Cited by 204 · see citing works
Adam, S. S., McDuffie, J. R., Ortel, T. L., & Williams, J. W. (2012) · Annals of Internal Medicine · doi:10.7326/0003-4819-157-10-201211200-00532 · Cited by 194 · see citing works
Desai, J., Kolb, J. M., Weitz, J. I., & Aisenberg, J. (2013) · Thrombosis and Haemostasis · doi:10.1160/th13-02-0150 · Cited by 192 · see citing works
Gastrointestinal bleeding in patients on novel oral anticoagulants: Risk, prevention and management
Cheung, K. S., & Leung, W. K. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i11.1954 · Cited by 190 · see citing works
de Werf, F. V., Brueckmann, M., Connolly, S. J., Friedman, J. E., Granger, C. B., Härtter, S., Harper, R., Kappetein, A. P., Lehr, T., Mack, M. J., et al. (2012) · American Heart Journal · doi:10.1016/j.ahj.2012.03.011 · Cited by 185 · see citing works
Gómez‐Outes, A., Terleira‐Fernández, A. I., Calvo, G., Suárez‐Gea, M. L., & Vargas, E. (2013) · Thrombosis · doi:10.1155/2013/640723 · Cited by 185 · see citing works
Dabigatran use in Danish atrial fibrillation patients in 2011: a nationwide study
Sørensen, R., Gislason, G., Torp-Pedersen, C. T., Olesen, J. B., Fosbøl, E. L., Hvidtfeldt, M. W., Karasoy, D., Lamberts, M., Charlot, M. G., Køber, L., et al. (2013) · BMJ Open · doi:10.1136/bmjopen-2013-002758 · Cited by 184 · see citing works
New Oral Anticoagulants and the Risk of Intracranial Hemorrhage
Chatterjee, S., Sardar, P., Biondi‐Zoccai, G., & Kumbhani, D. J. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.4021 · Cited by 184 · see citing works
Gastrointestinal Bleeding in Patients With Atrial Fibrillation Treated With Rivaroxaban or Warfarin
Sherwood, M. W., Nessel, C. C., Hellkamp, A. S., Mahaffey, K. W., Piccini, J. P., Suh, E., Becker, R. C., Singer, D. E., Halperin, J. L., Hankey, G. J., et al. (2015) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.09.024 · Cited by 184 · see citing works
Fibrinogen and Altered Hemostasis in Alzheimer's Disease
Cortés‐Canteli, M., Zamolodchikov, D., Ahn, H. J., Strickland, S., & Norris, E. H. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-120820 · Cited by 182 · see citing works
“Anticoagulant therapy as”
Maura, G., Blotière, P., Bouillon, K., Billionnet, C., Ricordeau, P., Alla, F., & Zureik, M. (2015) · Circulation · doi:10.1161/circulationaha.115.015710 · Cited by 174 · see citing works
Patti, G., Lucerna, M., Pecen, L., Siller-Matula, J. M., Cavallari, I., Kirchhof, P. F., & Caterina, R. D. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.117.005657 · Cited by 172 · see citing works
Yiin, G. S. C., Howard, D. P. J., Paul, N. L. M., Li, L., Luengo-Fernández, R., Bull, L. M., Welch, S. J. V., Gutnikov, S. A., Mehta, Z., & Rothwell, P. M. (2014) · Circulation · doi:10.1161/circulationaha.114.010942 · Cited by 169 · see citing works
Acute management of bleeding in patients on novel oral anticoagulants
Siegal, D. M., & Crowther, M. A. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs408 · Cited by 162 · see citing works
Factors Associated With Thrombotic Complications After the Fontan Procedure
McCrindle, B. W., Manlhiot, C., Cochrane, A. D., Roberts, R. E., Hughes, M. L., Szechtman, B., Weintraub, R. G., Andrew, M. E., & Monagle, P. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.08.1023 · Cited by 164 · see citing works
Bassiouny, M., Saliba, W. I., Rickard, J., Shao, M., Sey, A., Diab, M., Martin, D. O., Hussein, A. A., Khoury, M., Abi‐Saleh, B., et al. (2013) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.113.000320 · Cited by 164 · see citing works
“Interestingly, they reported an alarming 31% complication rate in this age group, which is consistent with recent published data suggesting increased risk of major bleeding in patients ≥75 years old with use of dabigatran 150 mg.(17) Thromboembolic complications occurred in 2% of patients on dabigatran and none in the…”
ResultAn update of consensus guidelines for warfarin reversal
Tran, H. A., Chunilal, S. D., Harper, P. L., Tran, H., Wood, E. M., & Gallus, A. S. (2013) · The Medical Journal of Australia · doi:10.5694/mja12.10614 · Cited by 164 · see citing works
Acutely Injured Patients on Dabigatran
Cotton, B. A., McCarthy, J. J., & Holcomb, J. B. (2011) · New England Journal of Medicine · doi:10.1056/nejmc1111095 · Cited by 161 · see citing works
Reilly, P. A., Bernstein, R. A., Dubiel, R., Eikelboom, J. W., Glund, S., Huisman, M. V., Hylek, E. M., Kam, C. W., Kamphuisen, P. W., Kreuzer, J., et al. (2015) · Thrombosis and Haemostasis · doi:10.1160/th15-03-0192 · Cited by 154 · see citing works
Olsen, A. S., Gislason, G., McGettigan, P., Fosbøl, E., Sørensen, R., Hansen, M. L., Køber, L., Torp-Pedersen, C., & Lamberts, M. (2015) · Journal of the American Medical Association (JAMA) · doi:10.1001/jama.2015.0809 · Cited by 153 · see citing works
Antithrombotic drugs and risk of hemorrhagic stroke in the general population
García-Rodríguez, L., Gaist, D., Morton, J., Cookson, C., & Gonzáléz-Pérez, A. (2013) · Neurology · doi:10.1212/wnl.0b013e31829e6ffa · Cited by 114 · see citing works
Diener, H., Aisenberg, J., Ansell, J., Atar, D., BREITHARDT, G. E., Eikelboom, J. W., Ezekowitz, M. D., Granger, C. B., Halperin, J. L., Hohnloser, S. H., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehv643 · Cited by 147 · see citing works
Zirlik, A., & Bode, C. (2016) · Journal of Thrombosis and Thrombolysis · doi:10.1007/s11239-016-1446-0 · Cited by 151 · see citing works
“a Intention-to-treat analysis b Data with additional events as per [34] or [33] or [43] c Primary efficacy endpoint in ENGAGE-AF was time to adjudicated stroke or systemic embolic event d Primary safety outcome in RE-LY and ARISTOTLE e Major or minor bleeding (minor bleeding was any bleeding not considered to be a maj…”
BackgroundStroke and Major Bleeding Risk in Elderly Patients Aged ≥75 Years With Atrial Fibrillation
Lip, G. Y. H., Clémenty, N., Pericart, L., Banerjee, A., & Fauchier, L. (2014) · Stroke · doi:10.1161/strokeaha.114.007199 · Cited by 141 · see citing works
Diener, H., Aisenberg, J., Ansell, J., Atar, D., BREITHARDT, G. E., Eikelboom, J. W., Ezekowitz, M. D., Granger, C. B., Halperin, J. L., Hohnloser, S. H., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw069 · Cited by 140 · see citing works
Kimachi, M., Furukawa, T. A., Kimachi, K., Goto, Y., Fukuma, S., & Fukuhara, S. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011373.pub2 · Cited by 143 · see citing works
Chiang, C., Wu, T.-J., Ueng, K.-C., Chao, T., Chang, K., Wang, C.-C., Lin, Y., Yin, W., Kuo, J., Lin, W., et al. (2016) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2016.10.005 · Cited by 138 · see citing works
Verheugt, F. W. A., & Granger, C. B. (2015) · The Lancet · doi:10.1016/s0140-6736(15)60245-8 · Cited by 134 · see citing works
Conway, S. E., Hwang, A. Y., Ponte, C. D., & Gums, J. G. (2016) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.1884 · Cited by 134 · see citing works
Lutz, J., Jurk, K., & Schinzel, H. (2017) · International Journal of Nephrology and Renovascular Disease · doi:10.2147/ijnrd.s105771 · Cited by 130 · see citing works
“3).(56) Dabigatran should not be used in patients with a GFR below 60 mL/min, although the US Food and Drug Administration approved dabigatran 75 mg twice daily in patients with a CrCl between 15 and 30 mL/min.”
JCS/JHRS 2020 Guideline on Pharmacotherapy of Cardiac Arrhythmias
Ono, K., Iwasaki, Y., Akao, M., Ikeda, T., Ishii, K., Inden, Y., Kusano, K., Kobayashi, Y., Koretsune, Y., Sasano, T., et al. (2022) · Circulation Journal · doi:10.1253/circj.cj-20-1212 · Cited by 132 · see citing works
Schnee, J. M., Fraeman, K. H., Siu, K., Reynolds, M. W., Collins, J. M., Schwartzman, E., & Villines, T. C. (2015) · Thrombosis and Haemostasis · doi:10.1160/th15-06-0453 · Cited by 125 · see citing works
“Descriptive data from the RE-LY trial indicate that patients on warfarin experienced higher frequencies of upper vs lower GI bleeding (75 % vs 25 %, respectively), while patients on dabigatran experienced approximately equal frequencies of upper vs lower GI bleeds (53 % vs 47 %, respectively) regardless of dose (24).”
BackgroundAdeboyeje, G., Sylwestrzak, G., Barron, J. J., White, J., Rosenberg, A., Abarca, J., Crawford, G., & Redberg, R. F. (2017) · Journal of Managed Care & Specialty Pharmacy · doi:10.18553/jmcp.2017.23.9.968 · Cited by 121 · see citing works
Hicks, T., Stewart, F. J., & Eisinga, A. (2016) · Open Heart · doi:10.1136/openhrt-2015-000279 · Cited by 119 · see citing works
Gorog, D. A., Gue, Y. X., Chao, T., Fauchier, L., Ferreiro, J. L., Huber, K., Konstantinides, S., Lane, D. A., Marín, F. R., Oldgren, J., et al. (2022) · Thrombosis and Haemostasis · doi:10.1055/s-0042-1750385 · Cited by 115 · see citing works
Olaf, M. F., & Cooney, R. R. (2017) · Emergency Medicine Clinics of North America · doi:10.1016/j.emc.2017.06.003 · Cited by 114 · see citing works
Baker, W. L., & Phung, O. J. (2012) · Circulation Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.112.966572 · Cited by 111 · see citing works
Periprocedural Management and Approach to Bleeding in Patients Taking Dabigatran
Weitz, J. I., Quinlan, D. J., & Eikelboom, J. W. (2012) · Circulation · doi:10.1161/circulationaha.112.123224 · Cited by 109 · see citing works
EHRA/EAPCI expert consensus statement on catheter-based left atrial appendage occlusion
Meier, B., Blaauw, Y., Khattab, A. A., Lewalter, T., Sievert, H., Tondo, C., & Glikson, M. (2015) · EuroIntervention · doi:10.4244/eijy14m09_18 · Cited by 109 · see citing works
Antithrombotic Therapy in Patients With Atrial Fibrillation Undergoing Coronary Stenting
Faxon, D. P., Eikelboom, J. W., Berger, P. B., Holmes, D. R., Bhatt, D. L., Moliterno, D. J., Becker, R. C., & Angiolillo, D. J. (2011) · Circulation Cardiovascular Interventions · doi:10.1161/circinterventions.111.965186 · Cited by 108 · see citing works
Landmesser, U., & Holmes, D. R. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr393 · Cited by 107 · see citing works
- Authors
- Eikelboom, J. W., Wallentin, L., Connolly, S. J., Ezekowitz, M., Healey, J. S., Oldgren, J., Yang, S., Alings, M., Kaatz, S., Hohnloser, S. H., Diener, H.-C., Franzosi, M. G., Huber, K., Reilly, P., Varrone, J., & Yusuf, S.
- Affiliations
- Goethe University Frankfurt (DE)
- ORCID
- Venue
- Circulation
- Published
- 2011-05-31
- Volume
- 123
- Issue
- 21
- Pages
- 2363-2372
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2064357176
- Cited by
- 1,081
- References
- 16
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 21 · 2023: 20 · 2022: 36 · 2021: 43 · 2020: 64 · 2019: 61 · 2018: 56 · 2017: 77 · 2016: 95 · 2015: 121 · 2014: 99 · 2013: 167 · 2012: 156
- FWCI
- 100.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Keywords
- dabigatran, warfarin, atrial fibrillation, major bleeding, intracranial hemorrhage, extracranial hemorrhage, stroke prevention, anticoagulation, elderly patients, age interaction, RE-LY trial, direct thrombin inhibitors, dose comparison, international normalized ratio, bleeding risk stratification, bleeding risk prediction model
- MeSH terms
- Dabigatran, Age Factors, Aged, Aged, 80 and over, Anticoagulants, Atrial Fibrillation, Benzimidazoles, Drug Administration Schedule, Female, Hemorrhage, Humans, Male, Middle Aged, Risk Factors, Time Factors, Warfarin, beta-Alanine
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