Long-Term Population-Based Cerebral Ischemic Event and Cognitive Outcomes of Direct Oral Anticoagulants Compared With Warfarin Among Long-term Anticoagulated Patients for Atrial Fibrillation

被引:125
作者
Jacobs, Victoria [1 ]
May, Heidi T. [1 ]
Bair, Tami L. [1 ]
Crandall, Brian G. [1 ]
Cutler, Michael J. [1 ]
Day, John D. [1 ]
Mallender, Charles [1 ]
Osborn, Jeffrey S. [1 ]
Stevens, Scott M. [1 ]
Weiss, J. Peter [1 ]
Woller, Scott C. [1 ]
Bunch, T. Jared [1 ]
机构
[1] Intermt Med Ctr, Intermt Heart Inst, Murray, UT 84157 USA
关键词
TRIAL; PREVENTION; DABIGATRAN; APIXABAN; DEMENTIA; EFFICACY; THERAPY; SAFETY; STROKE; RISK;
D O I
10.1016/j.amjcard.2016.04.039
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Direct oral anticoagulants (DOACs) have been used in clinical practice in the United States for the last 4 to 6 years. Although DOACs may be an attractive alternative to warfarin in many patients, long-term outcomes of use of these medications are unknown. We performed a propensity-matched analysis to report patient important outcomes of death, stroke/transient ischemic attack (TIA), bleeding, major bleeding, and dementia in patients taking a DOAC or warfarin. Patients receiving long-term anticoagulation from June 2010 to December 2014 for thromboembolism prevention with either warfarin or a DOAC were matched 1:1 by index date and propensity score. Multivariable Cox hazard regression was performed to determine the risk of death, stroke/TIA, major bleed, and dementia by the anticoagulant therapy received. A total of 5,254 patients were studied (2,627 per group). Average age was 72.4 +/- 10.9 years, and 59.0% were men. Most patients were receiving long-term anticoagulation for AF management (warfarin: 96.5% vs DOAC: 92.7%, p < 0.0001). Rivaroxaban (55.3%) was the most commonly used DOAC, followed by apixaban (22.5%) and dabigatran (22.2%). The use of DOACs compared with warfarin was associated with a reduced risk of long-term adverse outcomes: death (p = 0.09), stroke/TIA (p < 0.0001), major bleed (p < 0.0001), and bleed (p = 0.14). No significant outcome variance was noted in DOAC-type comparison. In the AF multivariable model patients taking DOAC were 43% less likely to develop stroke/TIA/dementia (hazard ratio 0.57 [CI 0.17, 1.97], p = 0.38) than those taking warfarin. Our community-based results suggest better long-term efficacy and safety of DOACs compared with warfarin. DOAC use was associated with a lower risk of cerebral ischemic events and new-onset dementia. (C) 2016 Elsevier Inc: All rights reserved.
引用
收藏
页码:210 / 214
页数:5
相关论文
共 19 条
[1]   A Randomized and Clinical Effectiveness Trial Comparing Two Pharmacogenetic Algorithms and Standard Care for Individualizing Warfarin Dosing (CoumaGen-II) [J].
Anderson, Jeffrey L. ;
Horne, Benjamin D. ;
Stevens, Scott M. ;
Woller, Scott C. ;
Samuelson, Kent M. ;
Mansfield, Justin W. ;
Robinson, Michelle ;
Barton, Stephanie ;
Brunisholz, Kim ;
Mower, Chrissa P. ;
Huntinghouse, John A. ;
Rollo, Jeffrey S. ;
Siler, Dustin ;
Bair, Tami L. ;
Knight, Stacey ;
Muhlestein, Joseph B. ;
Carlquist, John F. .
CIRCULATION, 2012, 125 (16) :1997-+
[2]   Atrial fibrillation is independently associated with senile, vascular, and Alzheimer's dementia [J].
Bunch, T. Jared ;
Weiss, J. Peter ;
Crandall, Brian G. ;
May, Heidi T. ;
Bair, Tami L. ;
Osborn, Jeffrey S. ;
Anderson, Jeffrey L. ;
Muhlestein, Joseph B. ;
Horne, Benjamin D. ;
Lappe, Donald L. ;
Day, John D. .
HEART RHYTHM, 2010, 7 (04) :433-437
[3]  
Christensen PS, 2014, EXP CLIN CARDIOL, V20, P5970
[4]   Apixaban in Patients with Atrial Fibrillation [J].
Connolly, Stuart J. ;
Eikelboom, John ;
Joyner, Campbell ;
Diener, Hans-Christoph ;
Hart, Robert ;
Golitsyn, Sergey ;
Flaker, Greg ;
Avezum, Alvaro ;
Hohnloser, Stefan H. ;
Diaz, Rafael ;
Talajic, Mario ;
Zhu, Jun ;
Pais, Prem ;
Budaj, Andrzej ;
Parkhomenko, Alexander ;
Jansky, Petr ;
Commerford, Patrick ;
Tan, Ru San ;
Sim, Kui-Hian ;
Lewis, Basil S. ;
Van Mieghem, Walter ;
Lip, Gregory Y. H. ;
Kim, Jae Hyung ;
Lanas-Zanetti, Fernando ;
Gonzalez-Hermosillo, Antonio ;
Dans, Antonio L. ;
Munawar, Muhammad ;
O'Donnell, Martin ;
Lawrence, John ;
Lewis, Gayle ;
Afzal, Rizwan ;
Yusuf, Salim .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (09) :806-817
[5]   Dabigatran versus Warfarin in Patients with Atrial Fibrillation. [J].
Connolly, Stuart J. ;
Ezekowitz, Michael D. ;
Yusuf, Salim ;
Eikelboom, John ;
Oldgren, Jonas ;
Parekh, Amit ;
Pogue, Janice ;
Reilly, Paul A. ;
Themeles, Ellison ;
Varrone, Jeanne ;
Wang, Susan ;
Alings, Marco ;
Xavier, Denis ;
Zhu, Jun ;
Diaz, Rafael ;
Lewis, Basil S. ;
Darius, Harald ;
Diener, Hans-Christoph ;
Joyner, Campbell D. ;
Wallentin, Lars .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (12) :1139-1151
[6]   Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial [J].
Easton, J. Donald ;
Lopes, Renato D. ;
Bahit, M. Cecilia ;
Wojdyla, Daniel M. ;
Granger, Christopher B. ;
Wallentin, Lars ;
Alings, Marco ;
Goto, Shinya ;
Lewis, Basil S. ;
Rosenqvist, Marten ;
Hanna, Michael ;
Mohan, Puneet ;
Alexander, John H. ;
Diener, Hans-Christoph .
LANCET NEUROLOGY, 2012, 11 (06) :503-511
[7]   Edoxaban versus Warfarin in Patients with Atrial Fibrillation [J].
Giugliano, Robert P. ;
Ruff, Christian T. ;
Braunwald, Eugene ;
Murphy, Sabina A. ;
Wiviott, Stephen D. ;
Halperin, Jonathan L. ;
Waldo, Albert L. ;
Ezekowitz, Michael D. ;
Weitz, Jeffrey I. ;
Spinar, Jindrich ;
Ruzyllo, Witold ;
Ruda, Mikhail ;
Koretsune, Yukihiro ;
Betcher, Joshua ;
Shi, Minggao ;
Grip, Laura T. ;
Patel, Shirali P. ;
Patel, Indravadan ;
Hanyok, James J. ;
Mercuri, Michele ;
Vogelmann, O. ;
Gonzalez, C. ;
Ahuad Guerrero, R. ;
Rodriguez, M. ;
Albisu, J. ;
Rosales, E. ;
Allall, O. ;
Reguero, M. ;
Alvarez, C. ;
Garcia, M. ;
Ameriso, S. ;
Ameriso, P. ;
Amuchastegui, M. ;
Caceres, M. ;
Beloscar, J. ;
Petrucci, J. ;
Berli, M. ;
Budassi, N. ;
Valle, M. ;
Bustamante Labarta, G. ;
Saravia, M. ;
Caccavo, A. ;
Fracaro, V. ;
Cartasegna, L. ;
Novas, V. ;
Caruso, O. ;
Saa Zarandon, R. ;
Colombo, H. ;
Morandini, M. ;
Cuello, J. .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (22) :2093-2104
[8]   Apixaban versus Warfarin in Patients with Atrial Fibrillation [J].
Granger, Christopher B. ;
Alexander, John H. ;
McMurray, John J. V. ;
Lopes, Renato D. ;
Hylek, Elaine M. ;
Hanna, Michael ;
Al-Khalidi, Hussein R. ;
Ansell, Jack ;
Atar, Dan ;
Avezum, Alvaro ;
Cecilia Bahit, M. ;
Diaz, Rafael ;
Easton, J. Donald ;
Ezekowitz, Justin A. ;
Flaker, Greg ;
Garcia, David ;
Geraldes, Margarida ;
Gersh, Bernard J. ;
Golitsyn, Sergey ;
Goto, Shinya ;
Hermosillo, Antonio G. ;
Hohnloser, Stefan H. ;
Horowitz, John ;
Mohan, Puneet ;
Jansky, Petr ;
Lewis, Basil S. ;
Luis Lopez-Sendon, Jose ;
Pais, Prem ;
Parkhomenko, Alexander ;
Verheugt, Freek W. A. ;
Zhu, Jun ;
Wallentin, Lars .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (11) :981-992
[9]   Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF [J].
Hankey, Graeme J. ;
Patel, Manesh R. ;
Stevens, Susanna R. ;
Becker, Richard C. ;
Breithardt, Gunter ;
Carolei, Antonio ;
Diener, Hans-Christoph ;
Donnan, Geoffrey A. ;
Halperin, Jonathan L. ;
Mahaffey, Kenneth W. ;
Mas, Jean-Louis ;
Massaro, Ayrton ;
Norrving, Bo ;
Nessel, Christopher C. ;
Paolini, John F. ;
Roine, Risto O. ;
Singer, Daniel E. ;
Wong, Lawrence ;
Califf, Robert M. ;
Fox, Keith A. A. ;
Hacke, Werner .
LANCET NEUROLOGY, 2012, 11 (04) :315-322
[10]   EHRA Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary [J].
Heidbuchel, Hein ;
Verhamme, Peter ;
Alings, Marco ;
Antz, Matthias ;
Hacke, Werner ;
Oldgren, Jonas ;
Sinnaeve, Peter ;
Camm, A. John ;
Kirchhof, Paulus .
EUROPEAN HEART JOURNAL, 2013, 34 (27) :2094-2106