Randomized Evaluation of Long Term Anticoagulant Therapy (RE-LY) With Dabigatran Etexilate

Summary

The primary objective of this trial is to demonstrate the efficacy and safety of dabigatran etexilate in patients with non-valvular atrial fibrillation for the prevention of stroke and systemic embolism.

Timeline

Start

2005-12

Primary completion

2009-04

Completion

—

Publications

• Hijazi Z, Lindback J, Oldgren J, Benz AP, Alexander JH, Connolly SJ, Eikelboom JW, Granger CB, Lopes RD, Siegbahn A, Wallentin L. Individual net clinical outcome with oral anticoagulation in atrial fibrillation using the ABC-AF risk scores. Am Heart J. 2023 Jul;261:55-63. doi: 10.1016/j.ahj.2023.03.012. Epub 2023 Mar 27.
• Reinhardt SW, Desai NR, Tang Y, Jones PG, Ader J, Spertus JA. Personalizing the decision of dabigatran versus warfarin in atrial fibrillation: A secondary analysis of the Randomized Evaluation of Long-term anticoagulation therapY (RE-LY) trial. PLoS One. 2021 Aug 19;16(8):e0256338. doi: 10.1371/journal.pone.0256338. eCollection 2021.
• Pol T, Hijazi Z, Lindback J, Oldgren J, Alexander JH, Connolly SJ, Eikelboom JW, Ezekowitz MD, Granger CB, Lopes RD, Yusuf S, Siegbahn A, Wallentin L. Using multimarker screening to identify biomarkers associated with cardiovascular death in patients with atrial fibrillation. Cardiovasc Res. 2022 Jul 20;118(9):2112-2123. doi: 10.1093/cvr/cvab262.
• Millenaar D, Schumacher H, Brueckmann M, Eikelboom JW, Ezekowitz M, Slawik J, Ewen S, Ukena C, Wallentin L, Connolly S, Yusuf S, Bohm M. Cardiovascular Outcomes According to Polypharmacy and Drug Adherence in Patients with Atrial Fibrillation on Long-Term Anticoagulation (from the RE-LY Trial). Am J Cardiol. 2021 Jun 15;149:27-35. doi: 10.1016/j.amjcard.2021.03.024. Epub 2021 Mar 20.
• Pol T, Hijazi Z, Lindback J, Alexander JH, Bahit MC, De Caterina R, Eikelboom JW, Ezekowitz MD, Gersh BJ, Granger CB, Hylek EM, Lopes R, Siegbahn A, Wallentin L. Evaluation of the prognostic value of GDF-15, ABC-AF-bleeding score and ABC-AF-death score in patients with atrial fibrillation across different geographical areas. Open Heart. 2021 Mar;8(1):e001471. doi: 10.1136/openhrt-2020-001471.
• Hijazi Z, Wallentin L, Lindback J, Alexander JH, Connolly SJ, Eikelboom JW, Ezekowitz MD, Granger CB, Lopes RD, Pol T, Yusuf S, Oldgren J, Siegbahn A. Screening of Multiple Biomarkers Associated With Ischemic Stroke in Atrial Fibrillation. J Am Heart Assoc. 2020 Dec 15;9(24):e018984. doi: 10.1161/JAHA.120.018984. Epub 2020 Dec 9.
• Wallentin L, Lindback J, Eriksson N, Hijazi Z, Eikelboom JW, Ezekowitz MD, Granger CB, Lopes RD, Yusuf S, Oldgren J, Siegbahn A. Angiotensin-converting enzyme 2 (ACE2) levels in relation to risk factors for COVID-19 in two large cohorts of patients with atrial fibrillation. Eur Heart J. 2020 Nov 1;41(41):4037-4046. doi: 10.1093/eurheartj/ehaa697.
• Bohm M, Brueckmann M, Eikelboom JW, Ezekowitz M, Frassdorf M, Hijazi Z, Hohnloser SH, Mahfoud F, Schmieder RE, Schumacher H, Wallentin L, Yusuf S. Cardiovascular outcomes, bleeding risk, and achieved blood pressure in patients on long-term anticoagulation with the thrombin antagonist dabigatran or warfarin: data from the RE-LY trial. Eur Heart J. 2020 Aug 7;41(30):2848-2859. doi: 10.1093/eurheartj/ehaa247.
• Stam-Slob MC, Connolly SJ, van der Graaf Y, van der Leeuw J, Dorresteijn JAN, Eikelboom JW, Peters RJG, Alings M, Visseren FLJ. Individual Treatment Effect Estimation of 2 Doses of Dabigatran on Stroke and Major Bleeding in Atrial Fibrillation. Circulation. 2019 Jun 18;139(25):2846-2856. doi: 10.1161/CIRCULATIONAHA.118.035266. Epub 2019 May 3.
• Hijazi Z, Verdecchia P, Oldgren J, Andersson U, Reboldi G, Di Pasquale G, Mazzotta G, Angeli F, Eikelboom JW, Ezekowitz MD, Connolly SJ, Yusuf S, Wallentin L. Cardiac Biomarkers and Left Ventricular Hypertrophy in Relation to Outcomes in Patients With Atrial Fibrillation: Experiences From the RE - LY Trial. J Am Heart Assoc. 2019 Jan 22;8(2):e010107. doi: 10.1161/JAHA.118.010107.
• Kent AP, Brueckmann M, Fraessdorf M, Connolly SJ, Yusuf S, Eikelboom JW, Oldgren J, Reilly PA, Wallentin L, Ezekowitz MD. Concomitant Oral Anticoagulant and Nonsteroidal Anti-Inflammatory Drug Therapy in Patients With Atrial Fibrillation. J Am Coll Cardiol. 2018 Jul 17;72(3):255-267. doi: 10.1016/j.jacc.2018.04.063. Epub 2018 Jul 9.
• Hijazi Z, Hohnloser SH, Oldgren J, Andersson U, Connolly SJ, Eikelboom JW, Ezekowitz MD, Reilly PA, Yusuf S, Wallentin L. Efficacy and safety of dabigatran compared with warfarin in patients with atrial fibrillation in relation to renal function over time-A RE-LY trial analysis. Am Heart J. 2018 Apr;198:169-177. doi: 10.1016/j.ahj.2017.10.015. Epub 2018 Jan 5. No abstract available.
• Hijazi Z, Oldgren J, Lindback J, Alexander JH, Connolly SJ, Eikelboom JW, Ezekowitz MD, Held C, Hylek EM, Lopes RD, Yusuf S, Granger CB, Siegbahn A, Wallentin L; ARISTOTLE and RE-LY Investigators. A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score. Eur Heart J. 2018 Feb 7;39(6):477-485. doi: 10.1093/eurheartj/ehx584.
• Verdecchia P, Reboldi G, Angeli F, Mazzotta G, Lip GYH, Brueckmann M, Kleine E, Wallentin L, Ezekowitz MD, Yusuf S, Connolly SJ, Di Pasquale G. Dabigatran vs. warfarin in relation to the presence of left ventricular hypertrophy in patients with atrial fibrillation- the Randomized Evaluation of Long-term anticoagulation therapY (RE-LY) study. Europace. 2018 Feb 1;20(2):253-262. doi: 10.1093/europace/eux022.
• Lauw MN, Eikelboom JW, Coppens M, Wallentin L, Yusuf S, Ezekowitz M, Oldgren J, Nakamya J, Wang J, Connolly SJ. Effects of dabigatran according to age in atrial fibrillation. Heart. 2017 Jul;103(13):1015-1023. doi: 10.1136/heartjnl-2016-310358. Epub 2017 Feb 17.
• Oldgren J, Hijazi Z, Lindback J, Alexander JH, Connolly SJ, Eikelboom JW, Ezekowitz MD, Granger CB, Hylek EM, Lopes RD, Siegbahn A, Yusuf S, Wallentin L; RE-LY and ARISTOTLE Investigators. Performance and Validation of a Novel Biomarker-Based Stroke Risk Score for Atrial Fibrillation. Circulation. 2016 Nov 29;134(22):1697-1707. doi: 10.1161/CIRCULATIONAHA.116.022802. Epub 2016 Aug 28.
• Ezekowitz MD, Nagarakanti R, Noack H, Brueckmann M, Litherland C, Jacobs M, Clemens A, Reilly PA, Connolly SJ, Yusuf S, Wallentin L. Comparison of Dabigatran and Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: The RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulant Therapy). Circulation. 2016 Aug 23;134(8):589-98. doi: 10.1161/CIRCULATIONAHA.115.020950. Epub 2016 Aug 5.
• Hijazi Z, Oldgren J, Lindback J, Alexander JH, Connolly SJ, Eikelboom JW, Ezekowitz MD, Held C, Hylek EM, Lopes RD, Siegbahn A, Yusuf S, Granger CB, Wallentin L; ARISTOTLE and RE-LY Investigators. The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study. Lancet. 2016 Jun 4;387(10035):2302-2311. doi: 10.1016/S0140-6736(16)00741-8. Epub 2016 Apr 4.
• Siegbahn A, Oldgren J, Andersson U, Ezekowitz MD, Reilly PA, Connolly SJ, Yusuf S, Wallentin L, Eikelboom JW. D-dimer and factor VIIa in atrial fibrillation - prognostic values for cardiovascular events and effects of anticoagulation therapy. A RE-LY substudy. Thromb Haemost. 2016 May 2;115(5):921-30. doi: 10.1160/TH15-07-0529. Epub 2016 Jan 28.
• Aulin J, Siegbahn A, Hijazi Z, Ezekowitz MD, Andersson U, Connolly SJ, Huber K, Reilly PA, Wallentin L, Oldgren J. Interleukin-6 and C-reactive protein and risk for death and cardiovascular events in patients with atrial fibrillation. Am Heart J. 2015 Dec;170(6):1151-60. doi: 10.1016/j.ahj.2015.09.018. Epub 2015 Oct 3.
• Brambatti M, Darius H, Oldgren J, Clemens A, Noack HH, Brueckmann M, Yusuf S, Wallentin L, Ezekowitz MD, Connolly SJ, Healey JS. Comparison of dabigatran versus warfarin in diabetic patients with atrial fibrillation: Results from the RE-LY trial. Int J Cardiol. 2015 Oct 1;196:127-31. doi: 10.1016/j.ijcard.2015.05.141. Epub 2015 May 28.
• Bohm M, Ezekowitz MD, Connolly SJ, Eikelboom JW, Hohnloser SH, Reilly PA, Schumacher H, Brueckmann M, Schirmer SH, Kratz MT, Yusuf S, Diener HC, Hijazi Z, Wallentin L. Changes in Renal Function in Patients With Atrial Fibrillation: An Analysis From the RE-LY Trial. J Am Coll Cardiol. 2015 Jun 16;65(23):2481-93. doi: 10.1016/j.jacc.2015.03.577.
• Hijazi Z, Oldgren J, Andersson U, Connolly SJ, Ezekowitz MD, Hohnloser SH, Reilly PA, Siegbahn A, Yusuf S, Wallentin L. Importance of persistent elevation of cardiac biomarkers in atrial fibrillation: a RE-LY substudy. Heart. 2014 Aug;100(15):1193-200. doi: 10.1136/heartjnl-2013-304872. Epub 2014 May 2.
• Verdecchia P, Reboldi G, Di Pasquale G, Mazzotta G, Ambrosio G, Yang S, Pogue J, Wallentin L, Ezekowitz MD, Connolly SJ, Yusuf S; RE-LY Study Investigators. Prognostic usefulness of left ventricular hypertrophy by electrocardiography in patients with atrial fibrillation (from the Randomized Evaluation of Long-Term Anticoagulant Therapy Study). Am J Cardiol. 2014 Feb 15;113(4):669-75. doi: 10.1016/j.amjcard.2013.10.045. Epub 2013 Nov 23.
• Hijazi Z, Hohnloser SH, Oldgren J, Andersson U, Connolly SJ, Eikelboom JW, Ezekowitz MD, Reilly PA, Siegbahn A, Yusuf S, Wallentin L. Efficacy and safety of dabigatran compared with warfarin in relation to baseline renal function in patients with atrial fibrillation: a RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) trial analysis. Circulation. 2014 Mar 4;129(9):961-70. doi: 10.1161/CIRCULATIONAHA.113.003628. Epub 2013 Dec 9.
• Majeed A, Hwang HG, Connolly SJ, Eikelboom JW, Ezekowitz MD, Wallentin L, Brueckmann M, Fraessdorf M, Yusuf S, Schulman S. Management and outcomes of major bleeding during treatment with dabigatran or warfarin. Circulation. 2013 Nov 19;128(21):2325-32. doi: 10.1161/CIRCULATIONAHA.113.002332. Epub 2013 Sep 30.
• Reilly PA, Lehr T, Haertter S, Connolly SJ, Yusuf S, Eikelboom JW, Ezekowitz MD, Nehmiz G, Wang S, Wallentin L; RE-LY Investigators. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol. 2014 Feb 4;63(4):321-8. doi: 10.1016/j.jacc.2013.07.104. Epub 2013 Sep 27.
• Marijon E, Le Heuzey JY, Connolly S, Yang S, Pogue J, Brueckmann M, Eikelboom J, Themeles E, Ezekowitz M, Wallentin L, Yusuf S; RE-LY Investigators. Causes of death and influencing factors in patients with atrial fibrillation: a competing-risk analysis from the randomized evaluation of long-term anticoagulant therapy study. Circulation. 2013 Nov 12;128(20):2192-201. doi: 10.1161/CIRCULATIONAHA.112.000491. Epub 2013 Sep 9.
• Eikelboom JW, Connolly SJ, Hart RG, Wallentin L, Reilly P, Oldgren J, Yang S, Yusuf S. Balancing the benefits and risks of 2 doses of dabigatran compared with warfarin in atrial fibrillation. J Am Coll Cardiol. 2013 Sep 3;62(10):900-8. doi: 10.1016/j.jacc.2013.05.042. Epub 2013 Jun 13.
• Hori M, Connolly SJ, Zhu J, Liu LS, Lau CP, Pais P, Xavier D, Kim SS, Omar R, Dans AL, Tan RS, Chen JH, Tanomsup S, Watanabe M, Koyanagi M, Ezekowitz MD, Reilly PA, Wallentin L, Yusuf S; RE-LY Investigators. Dabigatran versus warfarin: effects on ischemic and hemorrhagic strokes and bleeding in Asians and non-Asians with atrial fibrillation. Stroke. 2013 Jul;44(7):1891-6. doi: 10.1161/STROKEAHA.113.000990. Epub 2013 Jun 6.
• Pare G, Eriksson N, Lehr T, Connolly S, Eikelboom J, Ezekowitz MD, Axelsson T, Haertter S, Oldgren J, Reilly P, Siegbahn A, Syvanen AC, Wadelius C, Wadelius M, Zimdahl-Gelling H, Yusuf S, Wallentin L. Genetic determinants of dabigatran plasma levels and their relation to bleeding. Circulation. 2013 Apr 2;127(13):1404-12. doi: 10.1161/CIRCULATIONAHA.112.001233. Epub 2013 Mar 6.
• Dans AL, Connolly SJ, Wallentin L, Yang S, Nakamya J, Brueckmann M, Ezekowitz M, Oldgren J, Eikelboom JW, Reilly PA, Yusuf S. Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Circulation. 2013 Feb 5;127(5):634-40. doi: 10.1161/CIRCULATIONAHA.112.115386. Epub 2012 Dec 27.
• Bytzer P, Connolly SJ, Yang S, Ezekowitz M, Formella S, Reilly PA, Aisenberg J. Analysis of upper gastrointestinal adverse events among patients given dabigatran in the RE-LY trial. Clin Gastroenterol Hepatol. 2013 Mar;11(3):246-52.e1-5. doi: 10.1016/j.cgh.2012.10.021. Epub 2012 Oct 24.
• Van Spall HG, Wallentin L, Yusuf S, Eikelboom JW, Nieuwlaat R, Yang S, Kabali C, Reilly PA, Ezekowitz MD, Connolly SJ. Variation in warfarin dose adjustment practice is responsible for differences in the quality of anticoagulation control between centers and countries: an analysis of patients receiving warfarin in the randomized evaluation of long-term anticoagulation therapy (RE-LY) trial. Circulation. 2012 Nov 6;126(19):2309-16. doi: 10.1161/CIRCULATIONAHA.112.101808. Epub 2012 Oct 1.
• Healey JS, Eikelboom J, Douketis J, Wallentin L, Oldgren J, Yang S, Themeles E, Heidbuchel H, Avezum A, Reilly P, Connolly SJ, Yusuf S, Ezekowitz M; RE-LY Investigators. Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) randomized trial. Circulation. 2012 Jul 17;126(3):343-8. doi: 10.1161/CIRCULATIONAHA.111.090464. Epub 2012 Jun 14.
• Hijazi Z, Oldgren J, Andersson U, Connolly SJ, Ezekowitz MD, Hohnloser SH, Reilly PA, Vinereanu D, Siegbahn A, Yusuf S, Wallentin L. Cardiac biomarkers are associated with an increased risk of stroke and death in patients with atrial fibrillation: a Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) substudy. Circulation. 2012 Apr 3;125(13):1605-16. doi: 10.1161/CIRCULATIONAHA.111.038729. Epub 2012 Feb 28.
• Hohnloser SH, Oldgren J, Yang S, Wallentin L, Ezekowitz M, Reilly P, Eikelboom J, Brueckmann M, Yusuf S, Connolly SJ. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Circulation. 2012 Feb 7;125(5):669-76. doi: 10.1161/CIRCULATIONAHA.111.055970. Epub 2012 Jan 3.
• Oldgren J, Alings M, Darius H, Diener HC, Eikelboom J, Ezekowitz MD, Kamensky G, Reilly PA, Yang S, Yusuf S, Wallentin L, Connolly SJ; RE-LY Investigators. Risks for stroke, bleeding, and death in patients with atrial fibrillation receiving dabigatran or warfarin in relation to the CHADS2 score: a subgroup analysis of the RE-LY trial. Ann Intern Med. 2011 Nov 15;155(10):660-7, W204. doi: 10.7326/0003-4819-155-10-201111150-00004.
• Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J, Yang S, Alings M, Kaatz S, Hohnloser SH, Diener HC, Franzosi MG, Huber K, Reilly P, Varrone J, Yusuf S. 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. Circulation. 2011 May 31;123(21):2363-72. doi: 10.1161/CIRCULATIONAHA.110.004747. Epub 2011 May 16.
• Nagarakanti R, Ezekowitz MD, Oldgren J, Yang S, Chernick M, Aikens TH, Flaker G, Brugada J, Kamensky G, Parekh A, Reilly PA, Yusuf S, Connolly SJ. Dabigatran versus warfarin in patients with atrial fibrillation: an analysis of patients undergoing cardioversion. Circulation. 2011 Jan 18;123(2):131-6. doi: 10.1161/CIRCULATIONAHA.110.977546. Epub 2011 Jan 3.
• Ezekowitz MD, Wallentin L, Connolly SJ, Parekh A, Chernick MR, Pogue J, Aikens TH, Yang S, Reilly PA, Lip GY, Yusuf S; RE-LY Steering Committee and Investigators. Dabigatran and warfarin in vitamin K antagonist-naive and -experienced cohorts with atrial fibrillation. Circulation. 2010 Nov 30;122(22):2246-53. doi: 10.1161/CIRCULATIONAHA.110.973735.
• Diener HC, Connolly SJ, Ezekowitz MD, Wallentin L, Reilly PA, Yang S, Xavier D, Di Pasquale G, Yusuf S; RE-LY study group. Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial. Lancet Neurol. 2010 Dec;9(12):1157-1163. doi: 10.1016/S1474-4422(10)70274-X. Epub 2010 Nov 6.
• Wallentin L, Yusuf S, Ezekowitz MD, Alings M, Flather M, Franzosi MG, Pais P, Dans A, Eikelboom J, Oldgren J, Pogue J, Reilly PA, Yang S, Connolly SJ; RE-LY investigators. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet. 2010 Sep 18;376(9745):975-83. doi: 10.1016/S0140-6736(10)61194-4.
• Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. doi: 10.1056/NEJMoa0905561. Epub 2009 Aug 30.
• Ezekowitz MD, Connolly S, Parekh A, Reilly PA, Varrone J, Wang S, Oldgren J, Themeles E, Wallentin L, Yusuf S. Rationale and design of RE-LY: randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran. Am Heart J. 2009 May;157(5):805-10, 810.e1-2. doi: 10.1016/j.ahj.2009.02.005.

Drugs

Indications