Apixaban in patients with atrial fibrillation

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

doi:10.1056/nejmoa1007432

Cited by 2,483Atrial Fibrillation Management and OutcomesVenous Thromboembolism Diagnosis and ManagementAcute Ischemic Stroke Management

Apixaban in patients with atrial fibrillation

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Connolly, Stuart J., Eikelboom, John, Joyner, Campbell, Diener, Hans-Christoph, Hart, Robert, Golitsyn, Sergey, Flaker, Greg, Avezum, Alvaro +24 more·2011·New England Journal of Medicine

DOI 10.1056/nejmoa1007432

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Abstract

BACKGROUND: Vitamin K antagonists have been shown to prevent stroke in patients with atrial fibrillation. However, many patients are not suitable candidates for or are unwilling to receive vitamin K antagonist therapy, and these patients have a high risk of stroke. Apixaban, a novel factor Xa inhibitor, may be an alternative treatment for such patients. METHODS: In a double-blind study, we randomly assigned 5599 patients with atrial fibrillation who were at increased risk for stroke and for whom vitamin K antagonist therapy was unsuitable to receive apixaban (at a dose of 5 mg twice daily) or aspirin (81 to 324 mg per day), to determine whether apixaban was superior. The mean follow up period was 1.1 years. The primary outcome was the occurrence of stroke or systemic embolism. RESULTS: Before enrollment, 40% of the patients had used a vitamin K antagonist. The data and safety monitoring board recommended early termination of the study because of a clear benefit in favor of apixaban. There were 51 primary outcome events (1.6% per year) among patients assigned to apixaban and 113 (3.7% per year) among those assigned to aspirin (hazard ratio with apixaban, 0.45; 95% confidence interval [CI], 0.32 to 0.62; P<0.001). The rates of death were 3.5% per year in the apixaban group and 4.4% per year in the aspirin group (hazard ratio, 0.79; 95% CI, 0.62 to 1.02; P=0.07). There were 44 cases of major bleeding (1.4% per year) in the apixaban group and 39 (1.2% per year) in the aspirin group (hazard ratio with apixaban, 1.13; 95% CI, 0.74 to 1.75; P=0.57); there were 11 cases of intracranial bleeding with apixaban and 13 with aspirin. The risk of a first hospitalization for cardiovascular causes was reduced with apixaban as compared with aspirin (12.6% per year vs. 15.9% per year, P<0.001). The treatment effects were consistent among important subgroups. CONCLUSIONS: In patients with atrial fibrillation for whom vitamin K antagonist therapy was unsuitable, apixaban reduced the risk of stroke or systemic embolism without significantly increasing the risk of major bleeding or intracranial hemorrhage. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00496769.).

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OAC is superior to no treatment or aspirin in patients with different profiles for stroke risk.
“It is superior to no treatment or aspirin in patients with different profiles for stroke risk.”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [354]
Apixaban significantly reduced stroke or systemic embolism by 55% compared with aspirin, with no significant difference in rates of major bleeding or intracranial haemorrhage.
“apixaban significantly reduced stroke or systemic embolism by 55% compared with aspirin, with no significant difference in rates of major bleeding or intracranial haemorrhage.354,403”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [354]
Antiplatelet therapy increases bleeding risk, especially dual antiplatelet therapy (2.0% vs. 1.3% with antiplatelet monotherapy; P < 0.001), with bleeding rates that are similar to those on oral anticoagulation.
“Antiplatelet therapy increases bleeding risk, especially dual antiplatelet therapy (2.0% vs. 1.3% with antiplatelet monotherapy; P < 0.001), 433 with bleeding rates that are similar to those on OAC.354,362,431,434”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [354]

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Atrial fibrillation in patients with cryptogenic stroke
Gladstone, D. J., Spring, M., Dorian, P., Panzov, V., Thorpe, K. E., Hall, J., Vaid, H., O'Donnell, M., Laupacis, A., Côté, R., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1311376 · Cited by 1,276 · see citing works
2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation
Calkins, H. G., Hindricks, G., Cappato, R., Kim, Y., Saad, E., Aguinaga, L., Akar, J. G., Badhwar, V., Brugada, J., Camm, A. J., et al. (2017) · EP Europace · doi:10.1093/europace/eux274 · Cited by 1,191 · see citing works
“First, a direct thrombin or Factor Xa inhibitor can be administered several hours following ablation.(826,827,853,854) Second, low molecular weight heparin (enoxaparin 0.”
Background
2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation
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-citation
Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation
Heidbüchel, 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
Percutaneous Left Atrial Appendage Closure vs Warfarin for Atrial Fibrillation: A Randomized Clinical Trial
Reddy, V. Y., Sievert, H., Halperin, J., Doshi, S. K., Buchbinder, M., Neuzil, P., Huber, K., Whisenant, B., Kar, S., Swarup, V., et al. (2014) · JAMA · doi:10.1001/jama.2014.15192 · Cited by 1,018 · see citing works
Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome
Alexander, J. H., Lópes, R. D., James, S. K., Kilaru, R., He, Y., Mohan, P., Bhatt, D. L., Goodman, S. G., Verheugt, F. W. A., Flather, M. D., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1105819 · Cited by 1,002 · see citing works
Guidelines for the Prevention of Stroke in Women: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association
Bushnell, C., McCullough, L. D., Awad, I. A., Chireau, M. V., Fedder, W. N., Furie, K. L., Howard, V. J., Lichtman, J. H., Lisabeth, L. D., Piña, I. L., et al. (2014) · Stroke · doi:10.1161/01.str.0000442009.06663.48 · Cited by 941 · see citing works
Antithrombotic Therapy for Atrial Fibrillation
Lip, G. Y. H., Banerjee, A., Boriani, G., Chiang, C. E., Fargo, R. A., Freedman, B., Lane, D. A., Ruff, C. T., Turakhia, M. P., Werring, D. J., et al. (2018) · CHEST Journal · doi:10.1016/j.chest.2018.07.040 · Cited by 952 · see citing works
“The Apixaban Versus Acetylsalicylic Acid (ASA) to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trial compared apixaban 5 mg bid with aspirin in AF patients who were not candidates for VKA therapy.(125) The trial was stopped early for ben…”
Antithrombotic Therapy for Atrial Fibrillation
You, J. J., Singer, D. E., Howard, P. A., Lane, D. A., Eckman, M. H., Fang, M. C., Hylek, E. M., Schulman, S., Go, A. S., Hughes, M., et al. (2012) · CHEST Journal · doi:10.1378/chest.11-2304 · Cited by 924 · see citing works
2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation
Joglar, J. A., Chung, M. K., Armbruster, A. L., Benjamin, E. J., Chyou, J. Y., Cronin, E. M., Deswal, A., Eckhardt, L. L., Goldberger, Z. D., Gopinathannair, R., et al. (2024) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2023.08.017 · Cited by 933 · 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
Does the Left Atrial Appendage Morphology Correlate With the Risk of Stroke in Patients With Atrial Fibrillation?
Biase, L. D., Santangeli, P., Anselmino, M., Mohanty, P. K., Salvetti, I., Gili, S., Horton, R., Sánchez, J., Bai, R., Mohanty, S., et al. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.04.032 · Cited by 855 · see citing works
European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation
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
Left Atrial Appendage Closure With the Watchman Device in Patients With a Contraindication for Oral Anticoagulation
Reddy, V. Y., Möbius-Winkler, S., Miller, M. A., Neuzil, P., Schuler, G., Wiebe, J., Sick, P., & Sievert, H. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.03.035 · Cited by 727 · see citing works
“In the AVERROES (Apixaban Versus Acetylsalicylic Acid to Prevent Strokes in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment) study, warfarin-ineligible patients were randomly allocated to either aspirin or the factor Xa inhibitor, apixaban (21).”
Method
Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage
Frontera, J. A., Lewin, J. J., Rabinstein, A. A., Aisiku, I. P., Alexandrov, A. W., Cook, A. M., del Zoppo, G. J., Kumar, M. A., Peerschke, E. I. B., Stiefel, M., et al. (2015) · Neurocritical Care · doi:10.1007/s12028-015-0222-x · Cited by 713 · see citing works
“apixaban, and edoxaban), and secondary prevention of deep venous thrombosis or pulmonary embolism (rivaroxaban and apixaban only) [119–128].”
Background
A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa
Lu, G., DeGuzman, F. R., Hollenbach, S. J., Karbarz, M. J., Abe, K. Y., Lee, G., Luan, P., Hutchaleelaha, A., Inagaki, M., Conley, P. B., et al. (2013) · Nature Medicine · doi:10.1038/nm.3102 · Cited by 700 · see citing works
Percutaneous Left Atrial Appendage Closure for Stroke Prophylaxis in Patients With Atrial Fibrillation
Reddy, V. Y., Doshi, S. K., Sievert, H., Buchbinder, M., Neužil, P., Huber, K., Halperin, J. L., & Holmes, D. R. (2013) · Circulation · doi:10.1161/circulationaha.112.114389 · Cited by 677 · see citing works
Left Atrial Appendage Closure Versus Direct Oral Anticoagulants in High-Risk Patients With Atrial Fibrillation
Osmancik, P. P., Heřman, D., Neužil, P., Hála, P., Táborský, M., Kala, P., Poloczek, M., Šťásek, J., Haman, L., Branny, M., et al. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2020.04.067 · Cited by 654 · see citing works
Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment
Fox, K. A. A., Piccini, J. P., Wojdyla, D., Becker, R. C., Halperin, J. L., Nessel, C. C., Paolini, J. F., Hankey, G. J., Mahaffey, K. W., Patel, M. R., et al. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr342 · Cited by 608 · see citing works
“3) and seen in unselected clinical practice.(10,11,30) Those with moderate renal insufficiency have higher CHADS2 values than patients without renal dysfunction (Table 1), hence the importance of testing the randomized comparison of rivaroxaban and warfarin in a population that included a substantial cohort with moder…”
Background
Apixaban and dalteparin in active malignancy‐associated venous thromboembolism: The ADAM VTE trial
McBane, R. D., Wysokiński, W. E., Le‐Rademacher, J. G., Zemla, T., Ashrani, A. A., Tafur, A. J., Perepu, U. S., Anderson, D. M., Gundabolu, K., Kuzma, C. S., et al. (2019) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.14662 · Cited by 593 · see citing works
2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary
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) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.03.021 · Cited by 574 · see citing works
Emerging concepts in sporadic cerebral amyloid angiopathy
Charidimou, A., Boulouis, G., Gurol, M. E., Ayata, C., Bacskai, B. J., Frosch, M. P., Viswanathan, A., & Greenberg, S. M. (2017) · Brain · doi:10.1093/brain/awx047 · Cited by 555 · see citing works
“For example, apixaban has a similar intracranial bleeding risk profile as aspirin, but is more effective at reducing ischaemic stroke risk (Connolly et al., 2011).”
Background
Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS)
Task Force Members, Lip, G. Y. H., Windecker, S., Huber, K., Kirchhof, P. F., Marín, F. R., ten Berg, J. M., Hæusler, K. G., Boriani, G., Capodanno, D., et al. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu298 · Cited by 567 · see citing works
The 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Comprehensive Guidelines for the Management of Atrial Fibrillation
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
Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis
López-López, J. A., Sterne, J. A. C., Thom, H. H. Z., Higgins, J. P. T., Hingorani, A. D., Okoli, G. N., Davies, P. A., Bodalia, P. N., Bryden, P. A., Welton, N. J., et al. (2017) · BMJ · doi:10.1136/bmj.j5058 · Cited by 552 · see citing works
Apixaban versus Enoxaparin for Thromboprophylaxis in Medically Ill Patients
Goldhaber, S. Z., Leizorovicz, A., Kakkar, A. K., Haas, S. K., Merli, G. J., Knabb, R. M., & Weitz, J. I. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1110899 · Cited by 547 · see citing works
The Clinical Impact of Incomplete Left Atrial Appendage Closure With the Watchman Device in Patients With Atrial Fibrillation
Viles-González, J. F., Kar, S., Douglas, P. S., Dukkipati, S. R., Feldman, T. E., Horton, R., Holmes, D. R., & Reddy, V. Y. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.11.028 · Cited by 545 · see citing works
New Antithrombotic Drugs
Weitz, J. I., Eikelboom, J. W., & Samama, M. M. (2012) · CHEST Journal · doi:10.1378/chest.11-2294 · Cited by 533 · see citing works
Focused 2012 Update of the Canadian Cardiovascular Society Atrial Fibrillation Guidelines: Recommendations for Stroke Prevention and Rate/Rhythm Control
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
Off-Label Dosing of Non-Vitamin K Antagonist Oral Anticoagulants and Adverse Outcomes
Steinberg, B. A., Shrader, P. J., Thomas, L. E., Ansell, J., Fonarow, G. C., Gersh, B. J., Kowey, P. R., Mahaffey, K. W., Naccarelli, G. V., Reiffel, J. A., et al. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.09.966 · Cited by 493 · see citing works
2014 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation
Verma, A., Cairns, J. A., Mitchell, L. B., Macle, L., Stiell, I. G., Gladstone, D. J., McMurtry, M. S., Connolly, S. J., Cox, J. L., Dorian, P., et al. (2014) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2014.08.001 · Cited by 475 · see citing works
2021 Focused Update Consensus Guidelines of the Asia Pacific Heart Rhythm Society on Stroke Prevention in Atrial Fibrillation: Executive Summary
Chao, T., Joung, B., Takahashi, Y., Lim, T. W., Choi, E., Chan, Y., Guo, Y., Sriratanasathavorn, C., Oh, S., Okumura, K., et al. (2021) · Thrombosis and Haemostasis · doi:10.1055/s-0041-1739411 · Cited by 474 · see citing works
Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation
Healey, J. S., Lópes, R. D., Granger, C. B., Alings, M., Rivard, L., McIntyre, W. F., Atar, D., Birnie, D. H., Boriani, G., Camm, A. J., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2310234 · Cited by 460 · see citing works
Apixaban for Reduction In Stroke and Other ThromboemboLic Events in Atrial Fibrillation (ARISTOTLE) trial: Design and rationale
Lópes, R. D., Alexander, J. H., Al‐Khatib, S. M., Ansell, J., Diaz, R., Easton, J. D., Gersh, B. J., Granger, C. B., Hanna, M., Horowitz, J. D., et al. (2010) · American Heart Journal · doi:10.1016/j.ahj.2009.07.035 · Cited by 457 · see citing works
Net Clinical Benefit of Warfarin in Patients With Atrial Fibrillation: A Report From the Swedish Atrial Fibrillation Cohort Study
Friberg, L., Rosenqvist, M., & Lip, G. Y. H. (2012) · Circulation · doi:10.1161/circulationaha.111.055079 · Cited by 454 · see citing works
“Frequent falls, n (%) 9294 (10) 2647 (4) 0.”
Self-citation
Risk Profiles and Antithrombotic Treatment of Patients Newly Diagnosed with Atrial Fibrillation at Risk of Stroke: Perspectives from the International, Observational, Prospective GARFIELD Registry
Kakkar, A. K., Mueller, I., Bassand, J., Fitzmaurice, D. A., Goldhaber, S. Z., Goto, S., Haas, S. K., Hacke, W., Lip, G. Y. H., Mantovani, L. G., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0063479 · Cited by 444 · see citing works
“Despite mandating the presence of one or more additional stroke risk factors in an effort to exclude patients with lone AF, the GARFIELD population fares as relatively low risk compared with other observational cohorts, and is substantially lower risk than the populations included in randomized trials of novel oral an…”
2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure
Ponikowski, P. P., Voors, A. A., Anker, S. D., Bueno, H., Cleland, J. G. F., Coats, A. J. S., Falk, V., González‐Juanatey, J. R., Harjola, V., Jankowska, E. A., et al. (2016) · Kardiologia Polska · doi:10.5603/kp.2016.0141 · Cited by 450 · see citing works
Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study
Larsen, T. B., Skjøth, F., Nielsen, P. B., Kjældgaard, J. N., & Lip, G. Y. H. (2016) · BMJ · doi:10.1136/bmj.i3189 · Cited by 440 · see citing works
Cardioembolic Stroke
Kamel, H., & Healey, J. S. (2017) · Circulation Research · doi:10.1161/circresaha.116.308407 · Cited by 435 · see citing works
Dabigatran Association With Higher Risk of Acute Coronary Events
Uchino, K. (2012) · Archives of Internal Medicine · doi:10.1001/archinternmed.2011.1666 · Cited by 430 · see citing works
Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes
Kirchhof, P. F., Toennis, T., Goette, A., Camm, A. J., Diener, H., Becher, N., Bertaglia, E., Lundqvist, C. B., Borlich, M., Brandes, A., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2303062 · Cited by 442 · see citing works
New Oral Anticoagulants Increase Risk for Gastrointestinal Bleeding: A Systematic Review and Meta-analysis
Holster, I. L., Valkhoff, V. E., Kuipers, E. J., & Tjwa, E. T. T. L. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.02.041 · Cited by 407 · see citing works
EHRA Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary
Heidbüchel, 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
“There is good rationale for reducing the dose of NOACs in patients with a high bleeding risk and/or when a higher plasma level of the drug can be anticipated.(1,7,8) We have chosen an approach with three levels of alert for drug–drug interactions or other clinical factors that may affect NOAC plasma levels or effects…”
Background
2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation
January, C. T., Wann, L. S., Calkins, H. G., Chen, L. Y., Cigarroa, J. E., Cleveland, J. C., Ellinor, P. T., Ezekowitz, M. D., Field, M. E., Furie, K. L., et al. (2019) · Heart Rhythm · doi:10.1016/j.hrthm.2019.01.024 · Cited by 409 · see citing works
Atrial Fibrillation Catheter Ablation Versus Surgical Ablation Treatment (FAST): A 2-Center Randomized Clinical Trial
Boersma, L. V. A., Castella, M., van Boven, W., Berruezo, A., Yilmaz, A., Nadal, M., Sandoval, E., Calvo, N., Brugada, J., Kelder, J., et al. (2012) · Circulation · doi:10.1161/circulationaha.111.074047 · Cited by 396 · see citing works
Secondary stroke prevention
Hankey, G. J. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70255-2 · Cited by 392 · see citing works
Management of venous thrombo-embolism: an update
Konstantinides, S., & Torbicki, A. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu243 · Cited by 381 · see citing works
The AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke randomized trial: Rationale and methods
Kamel, H., Longstreth, W. T., Tirschwell, D., Kronmal, R. A., Broderick, J. P., Palesch, Y. Y., Meinzer, C., Dillon, C., Ewing, I., Spilker, J. A., et al. (2018) · International Journal of Stroke · doi:10.1177/1747493018799981 · Cited by 380 · see citing works
Antiplatelet Drugs
Eikelboom, J. W., Hirsh, J., Spencer, F. A., Baglin, T. P., & Weitz, J. I. (2012) · CHEST Journal · doi:10.1378/chest.11-2293 · Cited by 379 · see citing works
The Global Burden of Atrial Fibrillation and Stroke
Lip, G. Y. H., Brechin, C. M., & Lane, D. A. (2012) · CHEST Journal · doi:10.1378/chest.11-2888 · Cited by 376 · see citing works
Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial
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
Apixaban, an oral, direct factor X a inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects
Frost, C. E., Wang, J. J., Nepal, S., Schuster, A. E., Barrett, Y. C., Mosqueda‐Garcia, R., Reeves, R. A., & LaCreta, F. P. (2012) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2012.04369.x · Cited by 368 · see citing works
Parenteral anticoagulants in heart disease: Current status and perspectives (Section II)
Husted, S., Wallentin, L. C., Andreotti, F., Arnesen, H., Bachmann, F., Baigent, C., Huber, K., Jespersen, J., Kristensen, S. D., Lip, G. Y. H., et al. (2013) · Thrombosis and Haemostasis · doi:10.1160/th12-06-0403 · Cited by 366 · see citing works
Variations in Cause and Management of Atrial Fibrillation in a Prospective Registry of 15 400 Emergency Department Patients in 46 Countries
Oldgren, J., Healey, J. S., Ezekowitz, M. D., Commerford, P., Avezum, Á., Pais, P. S., Zhu, J., Janský, P., Sigamani, A., Morillo, C. A., et al. (2014) · Circulation · doi:10.1161/circulationaha.113.005451 · Cited by 366 · see citing works
“From the Uppsala Clinical Research Center and Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden (J.O., L.W.); Population Health Research Institute, Hamilton, Ontario, Canada (J.S.H., C.A.M., A.G., J.N., S.J.C., S.Y.); Jefferson Medical College, Wynnewood, PA, and Cardiovascular Research F…”
BackgroundInfluential
EHRA/EAPCI expert consensus statement on catheter-based left atrial appendage occlusion – an update
Glikson, M., Wolff, R., Hindricks, G., Mandrola, J. M., Camm, A. J., Lip, G. Y. H., Fauchier, L., Betts, T. R., Lewalter, T., Saw, J., et al. (2020) · EuroIntervention · doi:10.4244/eijy19m08_01 · Cited by 366 · see citing works
Atrial fibrillation in heart failure: what should we do?
Kotecha, D., & Piccini, J. P. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv513 · Cited by 371 · see citing works
Primary and Secondary Prevention of Ischemic Stroke and Cerebral Hemorrhage
Diener, H., & Hankey, G. J. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.12.072 · Cited by 366 · see citing works
Vitamin K antagonists in heart disease: Current status and perspectives (Section III)
Husted, S., Wallentin, L. C., Andreotti, F., Arnesen, H., Bachmann, F., Baigent, C., Huber, K., Jespersen, J., Kristensen, S. D., Lip, G. Y. H., et al. (2013) · Thrombosis and Haemostasis · doi:10.1160/th13-06-0443 · Cited by 367 · see citing works
Interventional Spine and Pain Procedures in Patients on Antiplatelet and Anticoagulant Medications
Narouze, S., Benzon, H. T., Provenzano, D. A., Buvanendran, A., Andrés, J. A. D., Deer, T. R., Rauck, R. L., & Huntoon, M. A. (2015) · Regional Anesthesia & Pain Medicine · doi:10.1097/aap.0000000000000223 · Cited by 364 · see citing works
Clinical outcomes in systematic screening for atrial fibrillation (STROKESTOP): a multicentre, parallel group, unmasked, randomised controlled trial
Svennberg, E., Friberg, L., Frykman, V., Al‐Khalili, F., Engdahl, J., & Rosenqvist, M. (2021) · The Lancet · doi:10.1016/s0140-6736(21)01637-8 · Cited by 366 · see citing works
Apixaban: A Clinical Pharmacokinetic and Pharmacodynamic Review
Byon, W., Merali, S. J., Boyd, R. A., & Frost, C. E. (2019) · Clinical Pharmacokinetics · doi:10.1007/s40262-019-00775-z · Cited by 356 · see citing works
Dabigatran Etexilate
Hankey, G. J., & Eikelboom, J. W. (2011) · Circulation · doi:10.1161/circulationaha.110.004424 · Cited by 348 · see citing works
Atrial fibrillation
Lip, G. Y. H., Tse, H., & Lane, D. A. (2011) · The Lancet · doi:10.1016/s0140-6736(11)61514-6 · Cited by 341 · see citing works
EHRA/EAPCI expert consensus statement on catheter-based left atrial appendage occlusion – an update
Glikson, M., Wolff, R., Hindricks, G., Mandrola, J. M., Camm, A. J., Lip, G. Y. H., Fauchier, L., Betts, T. R., Lewalter, T., Saw, J., et al. (2019) · EP Europace · doi:10.1093/europace/euz258 · Cited by 332 · see citing works
National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand: Australian Clinical Guidelines for the Diagnosis and Management of Atrial Fibrillation 2018
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Apixaban versus warfarin in patients with atrial fibrillation
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Abstract 3776: Apixaban Compared To Aspirin In Patients With Atrial Fibrillation And Prior Transient Ischemic Attack Or Stroke: Results Of A Predefined Subgroup Analysis From Averroes
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900 Efficacy and safety of apixaban compared to warfarin for prevention of stroke and systemic embolism in 18,201 patients with atrial fibrillation: Primary results of the ARISTOTLE Trial
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Apixaban versus aspirin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a predefined subgroup analysis from AVERROES, a randomised trial
Lawrence, J., Pogue, J., Synhorst, D., Adalet, K., Atar, D., Avezum, A., Budaj, A. M., Commerford, P., Dans, A. L., De Caterina, R., et al. (2012) · CINECA IRIS Institutial research information system (University of Pisa)

Authors: Connolly, S. J., Eikelboom, J., Joyner, C., Diener, H.-C., Hart, R., Golitsyn, S., Flaker, G., Avezum, A., Hohnloser, S. H., Diaz, R., Talajic, M., Zhu, J., Pais, P., Budaj, A., Parkhomenko, A., Jansky, P., Commerford, P., Tan, R. S., Sim, K.-H., Lewis, B. S., Van Mieghem, W., Lip, G. Y. H., Kim, J. H., Lanas-Zanetti, F., Gonzalez-Hermosillo, A., Dans, A. L., Munawar, M., O'Donnell, M., Lawrence, J., Lewis, G., Afzal, R., & Yusuf, S.
Affiliations: Population Health Research Institute (CA)
ORCID: Connolly, Stuart J.
Eikelboom, John
Hart, Robert
Hohnloser, Stefan H.
Talajic, Mario
Zhu, Jun
Budaj, Andrzej
Parkhomenko, Alexander
Tan, Ru San
Lewis, Basil S.
Lip, Gregory Y.H.
O'Donnell, Martin
Lawrence, John
Yusuf, Salim
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2011-03-03
Volume: 364
Issue: 9
Pages: 806-817
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa1007432
OpenAlex: W2149388786
Cited by: 2,483
References: 23
Citations by year: 2026: 45 · 2025: 54 · 2024: 99 · 2023: 70 · 2022: 71 · 2021: 111 · 2020: 111 · 2019: 119 · 2018: 139 · 2017: 172 · 2016: 215 · 2015: 239 · 2014: 249 · 2013: 310 · 2012: 303
FWCI: 223.65
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
UWA Profiles and Research Repository (UWA) (submittedVersion)
Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
UnissResearch (Università degli Studi di Sassari) (submittedVersion)
Omeka S (Universidad de La Frontera) (submittedVersion)
Funders: Bristol-Myers Squibb
Eli Lilly and Company
Pfizer
AstraZeneca
GlaxoSmithKline
Sanofi
Hamilton Health Sciences
McMaster University
Astellas Pharma
Servier
Institut de Cardiologie de Montréal
St. Jude Medical
Bayer Vital
Cilag
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: apixaban, atrial fibrillation, factor Xa inhibitors, aspirin, stroke prevention, systemic embolism, vitamin K antagonists, major bleeding, intracranial hemorrhage, cardiovascular hospitalization, oral anticoagulation, early trial termination, cardiovascular mortality, cardiovascular risk stratification, subgroup analysis, bleeding risk stratification
MeSH terms: Aged, Aged, 80 and over, Aspirin, Atrial Fibrillation, Double-Blind Method, Embolism, Female, Fibrinolytic Agents, Hemorrhage, Humans, Male, Middle Aged, Pyrazoles, Pyridones, Risk Factors, Proportional Hazards Models, Stroke, Factor Xa Inhibitors

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