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Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation (ARISTOTLE)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00412984
First Posted: December 19, 2006
Last Update Posted: November 7, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Bristol-Myers Squibb
  Purpose
The trial seeks to determine if apixaban, an investigational anticoagulant (blood-thinner) is as effective as standard therapy (warfarin) in preventing stroke and systemic embolism in subjects with atrial fibrillation and risk factors for stroke.

Condition Intervention Phase
Atrial Fibrillation Atrial Flutter Drug: warfarin Drug: apixaban Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: A Phase 3, Active (Warfarin) Controlled, Randomized, Double-Blind, Parallel Arm Study to Evaluate Efficacy and Safety of Apixaban in Preventing Stroke and Systemic Embolism in Subjects With Nonvalvular Atrial Fibrillation

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Number of Participants With First Event of Ischemic/Unspecified Stroke, Hemorrhagic Stroke, or Systemic Embolism (SE) During the Intended Treatment Period [ Time Frame: Time to first event in "Intended Treatment Period": started on day of randomization, ended at efficacy cut-off date (date target number of primary efficacy events [448] was expected to have occurred; set to 30-Jan-2011, prior to unblinding). ]
    All suspected efficacy events were adjudicated by the Central Events Committee (CEC). Diagnosis of stroke=the nontraumatic focal neurological deficit lasting at least 24 hours, and includes ischemic stroke, hemorrhagic stroke, ischemic stroke with hemorrhagic conversion, stroke of uncertain type, and retinal ischemic event (embolism, infarction). Diagnosis of SE=clinical history consistent with an acute loss of blood flow to a peripheral artery (or arteries), supported by evidence of embolism from surgical specimens, autopsy, angiography, vascular imaging, or other objective testing.

  • Rate of Adjudicated Stroke or Systemic Embolism (SE) During the Intended Treatment Period [ Time Frame: "Intended Treatment Period" started on the day of randomization and ended at the efficacy cut-off date (date on which it was expected that the target number of primary efficacy events [448] would have occurred; set to 30-Jan-2011, prior to unblinding). ]
    Rate=Number of adjudicated stroke or SE events per 100 patient years. Diagnosis of stroke=the nontraumatic focal neurological deficit lasting at least 24 hours, and includes ischemic stroke, hemorrhagic stroke, ischemic stroke with hemorrhagic conversion, stroke of uncertain type, and retinal ischemic event (embolism, infarction). Diagnosis of SE=clinical history consistent with an acute loss of blood flow to a peripheral artery (or arteries), supported by evidence of embolism from surgical specimens, autopsy, angiography, vascular imaging, or other objective testing.

  • Number of Participants With Event of Major (International Society on Thrombosis and Hemostasis [ISTH]) Bleeding During Treatment Period [ Time Frame: "Treatment Period" started with first dose of blinded study drug and ended 2 days after the last dose of blinded study drug. Mean duration of exposure to double-blind study drug was 1.7 years in each treatment group. ]
    ISTH Bleeding Criteria: Major bleeding=a bleeding event that was: clinically overt bleeding accompanied by a decrease in hemoglobin (Hgb) of 2 g/dL or more over a 24-hour period and/or a transfusion of 2 or more units of packed red blood cells; bleeding that occurred in at least 1 of the following critical sites: intracranial, intraspinal, intraocular (within the corpus of the eye; a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, and retroperitoneal; bleeding that was fatal.

  • Rate of Adjudicated Major (ISTH) Bleed Events During Treatment Period [ Time Frame: "Treatment Period" started with first dose of blinded study drug and ended 2 days after the last dose of blinded study drug. Mean duration of exposure to double-blind study drug was 1.7 years in each treatment group. ]
    Rate=number of adjudicated major (ISTH) bleed events per 100 patient years. ISTH Bleeding Criteria: Major bleeding=a bleeding event that was: clinically overt bleeding accompanied by a decrease in hemoglobin (Hgb) of 2 g/dL or more and/or a transfusion of 2 or more units of packed red blood cells; bleeding that occurred in at least 1 of the following sites: intracranial, intraspinal, intraocular (within the corpus of the eye; a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, and retroperitoneal; bleeding that was fatal.


Secondary Outcome Measures:
  • Number of Participants With Events of All-Cause Death During the Intended Treatment Period [ Time Frame: "Intended Treatment Period" started on the day of randomization and ended at the efficacy cut-off date (date on which it was expected that the target number of primary efficacy events [448] would have occurred; set to 30-Jan-2011, prior to unblinding). ]
    Death was defined as all-cause mortality. All unobserved deaths were assumed to be cardiovascular in nature unless a non-cardiovascular cause could be clearly provided. Cardiovascular=deaths due to ischemic and hemorrhagic stroke, SE, myocardial infarction (MI), sudden death, heart failure, other cardiovascular, and unobserved deaths. Non-cardiovascular=all deaths due to a clearly documented non-cardiovascular cause (further classified into the categories: bleeding, study drug toxicity other than bleeding, malignancy, infection, trauma, and pulmonary causes of death).

  • Rate of Adjudicated All-Cause Death During the Intended Treatment Period [ Time Frame: "Intended Treatment Period" started on the day of randomization and ended at the efficacy cut-off date (date on which it was expected that the target number of primary efficacy events [448] would have occurred; set to 30-Jan-2011, prior to unblinding). ]
    All unobserved deaths were assumed to be cardiovascular in nature unless a non-cardiovascular cause could be clearly provided. Cardiovascular=deaths due to ischemic and hemorrhagic stroke, SE, MI, sudden death, heart failure, other cardiovascular, and unobserved deaths. Non-cardiovascular=all deaths due to a clearly documented non-cardiovascular cause (further classified into the categories: bleeding, study drug toxicity other than bleeding, malignancy, infection, trauma, and pulmonary causes of death).

  • Rate of Ischemic or Unspecified Stroke, Hemorrhagic Stroke, Systemic Embolism (SE), and Myocardial Infarction (MI) (as Individual Endpoints) During the Intended Treatment Period [ Time Frame: "Intended Treatment Period" started on the day of randomization and ended at the efficacy cut-off date (date on which it was expected that the target number of primary efficacy events [448] would have occurred; set to 30-Jan-2011, prior to unblinding). ]
    Diagnosis for an acute or evolving MI=elevation of creatine kinase-MB isoenzyme (CK-MB) or Troponin T or I ≥ 2 × the upper limit of normal (ULN), or if no CK-MB or troponin values are available, a total CK ≥ 2×ULN, or new, significant (≥0.04 s) Q waves in ≥2 contiguous leads. For descriptions of Stroke and SE, see Outcome Measure 1.

  • Rate of Ischemic or Unspecified Stroke, Hemorrhagic Stroke, Systemic Embolism (SE), Myocardial Infarction (MI) and All-Cause Death (ACD) (as Composite Endpoints) During the Intended Treatment Period [ Time Frame: "Intended Treatment Period" started on the day of randomization and ended at the efficacy cut-off date (date on which it was expected that the target number of primary efficacy events [448] would have occurred; set to 30-Jan-2011, prior to unblinding). ]
    Diagnosis for an acute or evolving MI=elevation of CK-MB or Troponin T or I ≥ 2 × the ULN, or if no CK-MB or troponin values are available, a total CK ≥ 2×ULN, or new, significant (≥0.04 s) Q waves in ≥2 contiguous leads. For descriptions of Stroke and SE, see Outcome Measure 1. For description of ACD, see Outcome Measure 5.

  • Number of Warfarin/Vitamin K Antagonist (VKA) Naive Participants With Composite Stroke / Systemic Embolism (SE) / Major Bleeding During the Intended Treatment Period [ Time Frame: "Intended Treatment Period" started on the day of randomization and ended at the efficacy cut-off date (date on which it was expected that the target number of primary efficacy events [448] would have occurred; set to 30-Jan-2011, prior to unblinding). ]
    For descriptions of Stroke and SE, see Outcome Measure 1. For description of Major bleeding, see Outcome Measure 3.

  • Rate of Composite Stroke / Systemic Embolism / Major Bleeding in Warfarin/Vitamin K Antagonist (VKA) Naive Participants During the Intended Treatment Period [ Time Frame: "Intended Treatment Period" started on the day of randomization and ended at the efficacy cut-off date (date on which it was expected that the target number of primary efficacy events [448] would have occurred; set to 30-Jan-2011, prior to unblinding). ]
  • Number of Participants With Events of Major or Clinically Relevant Nonmajor (CRNM) Bleed During Treatment Period [ Time Frame: "Treatment Period" started with first dose of blinded study drug and ended 2 days after the last dose of blinded study drug. Mean duration of exposure to double-blind study drug was 1.7 years in each treatment group. ]
    Major bleeding=bleeding that is clinically overt and that either resulted in a decrease in hemoglobin of 2 g/dL or more over a 24-hour period, led to a transfusion of 2 or more units of packed red blood cells, occurred in a critical site, or led to death. CRNM bleeding=bleeding that is clinically overt, that satisfies none of the additional criteria required for the event to be adjudicated as a major bleeding event, that led to either hospital admission for bleeding, physician-guided medical or surgical treatment for bleeding, or a change in antithrombotic therapy.

  • Rate of Events of Major or Clinically Relevant Non-Major (CRNM) Bleed During Treatment Period [ Time Frame: "Treatment Period" started with first dose of blinded study drug and ended 2 days after the last dose of blinded study drug. Mean duration of exposure to double-blind study drug was 1.7 years in each treatment group. ]
    Rate=number of major or CRNM bleed events per 100 patient years. Major=clinically overt and either 1) resulted in a decrease in hemoglobin of 2 g/dL or more over a 24-hour period, or 2) led to a transfusion of 2 or more units of packed red blood cells, or 3) occurred in a critical site, or 4) led to death. CRNM bleeding=clinically overt, but satisfied no additional criteria required to be adjudicated as a major bleeding event, and led to either 1) hospital admission for bleeding or 2) physician guided medical or surgical treatment for bleeding or 3) a change in antithrombotic therapy.

  • Number of Participants With All Bleeding Events During Treatment Period [ Time Frame: "Treatment Period" started with first dose of blinded study drug and ended 2 days after the last dose of blinded study drug. Mean duration of exposure to double-blind study drug was 1.7 years in each treatment group. ]
    All bleeding events include major bleeding, CRNM bleeding (see Outcome Measure 12 Description for definitions), plus events of minor bleeding and fatal bleeding. Minor bleeding: All acute clinically overt bleeding events not meeting the criteria for either major bleeding or clinically relevant non-major bleeding will be classified as minor bleeding. Fatal bleeding is defined as a bleeding event that the Clinical Events Committee determines is the primary cause of death or contributes directly to death.

  • Rate of All Bleeding Events During Treatment Period [ Time Frame: "Treatment Period" started with first dose of blinded study drug and ended 2 days after the last dose of blinded study drug. Mean duration of exposure to double-blind study drug was 1.7 years in each treatment group. ]
    Rate=number of all bleeding events per 100 patient years. "All bleeding events" include major bleeding, CRNM bleeding (see Outcome Measure 12 Description for definitions), plus events of minor bleeding and fatal bleeding. Minor bleeding: All acute clinically overt bleeding events not meeting the criteria for either major bleeding or clinically relevant non-major bleeding will be classified as minor bleeding. Fatal bleeding is defined as a bleeding event that the Clinical Events Committee determines is the primary cause of death or contributes directly to death.


Other Outcome Measures:
  • Number of Participants With Adverse Events (AEs), Bleeding AEs, Serious Adverse Events (SAEs), Discontinuations Due to AEs, or Deaths During the Treatment Period [ Time Frame: "Treatment Period" started with first dose of blinded study drug and ended 2 days after the last dose of blinded study drug. Mean duration of exposure to double-blind study drug was 1.7 years in each treatment group. ]
    AE: all SAEs or AEs with onset from first dose through 2 days (AEs) or 30 days (SAEs) after the last dose of blinded study drug (BSD). SAE: all SAEs with onset from first dose through 30 days after the last dose of BSD. Bleeding AE: all serious or non-serious bleeding-related AEs with onset from first dose through 2 days after the last dose of BSD. Discontinuations due to AE: all SAEs or AEs with onset from first dose of BSD and with action taken=drug discontinued. Deaths: all deaths occurring from first dose through 30 days after the last dose of BSD.

  • Rate of Adjudicated Bleeding Endpoints Per Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) During the Treatment Period [ Time Frame: "Treatment Period" started with first dose of blinded study drug and ended 2 days after the last dose of blinded study drug. Mean duration of exposure to double-blind study drug was 1.7 years in each treatment group. ]
    Rate=number of adjudicated GUSTO bleeding events per 100 patient years. GUSTO Bleeding Criteria: GUSTO severe (or life-threatening) bleeding: either intracranial hemorrhage or bleeding that causes hemodynamic compromise and requires intervention. GUSTO moderate bleeding: bleeding that requires blood transfusion but does not result in hemodynamic compromise.

  • Rate of Adjudicated Bleeding Endpoints Per Thrombolysis in Myocardial Infarction (TIMI) During the Treatment Period [ Time Frame: "Treatment Period" started with first dose of blinded study drug and ended 2 days after the last dose of blinded study drug. Mean duration of exposure to double-blind study drug was 1.7 years in each treatment group. ]
    Rate=number of adjudicated TIMI bleeding events per 100 patient years. TIMI Bleeding Criteria: Major bleeding=Intracranial bleeding and/or clinically overt bleeding associated with ≥5 gm/dL fall in Hgb or 15% fall in hematocrit (Hct) from baseline, accounting for transfusions. Minor bleeding=Clinically overt bleeding associated with ≥3 gm/dL fall in Hgb or a ≥10% fall in Hct from baseline, accounting for transfusions.

  • Number of Participants With Net-Clinical Benefit During Treatment Period [ Time Frame: "Treatment Period" started with first dose of blinded study drug and ended 2 days after the last dose of blinded study drug. Mean duration of exposure to double-blind study drug was 1.7 years in each treatment group. ]
    Net-Clinical Benefit = Composite of stroke, systemic embolism and ISTH major bleeding.

  • Rate of Net-Clinical Benefit During Treatment Period [ Time Frame: "Treatment Period" started with first dose of blinded study drug and ended 2 days after the last dose of blinded study drug. Mean duration of exposure to double-blind study drug was 1.7 years in each treatment group. ]
    Rate=number of events of net-clinical benefit per 100 patient years. Net-Clinical Benefit = Composite of stroke, systemic embolism and ISTH major bleeding


Enrollment: 18201
Study Start Date: December 2006
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 Drug: warfarin
Oral tablets, 2.0 mg, adjusted to an INR of 2.5 (range 2.0 to 3.0)
Other Names:
  • Coumadin
  • BMS-565793
Experimental: 2 Drug: apixaban
Oral tablets, 5.0 mg or 2.5 mg, twice daily
Other Name: BMS-562247

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females ≥ 18 yrs with atrial fibrillation (AF) and one or more of the following risk factors for stroke:
  • Age ≥ 75, previous stroke
  • transient ischemic attack (TIA) or Systemic Embolism (SE)
  • Symptomatic congestive heart failure or left ventricular dysfunction with left ventricular ejection fraction (LVEF) ≤ 40%
  • Diabetes mellitus or hypertension requiring pharmacological treatment
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00412984


  Show 1012 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Hu PT, Lopes RD, Stevens SR, Wallentin L, Thomas L, Alexander JH, Hanna M, Lewis BS, Verheugt FW, Granger CB, Jones WS. Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation and Peripheral Artery Disease: Insights From the ARISTOTLE Trial. J Am Heart Assoc. 2017 Jan 17;6(1). pii: e004699. doi: 10.1161/JAHA.116.004699.
Oldgren J, Hijazi Z, Lindbäck 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. Epub 2016 Aug 28.
Alexander JH, Andersson U, Lopes RD, Hijazi Z, Hohnloser SH, Ezekowitz JA, Halvorsen S, Hanna M, Commerford P, Ruzyllo W, Huber K, Al-Khatib SM, Granger CB, Wallentin L; Apixaban for Reduction of Stroke and Other Thromboembolic Complications in Atrial Fibrillation (ARISTOTLE) Investigators. Apixaban 5 mg Twice Daily and Clinical Outcomes in Patients With Atrial Fibrillation and Advanced Age, Low Body Weight, or High Creatinine: A Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2016 Sep 1;1(6):673-81. doi: 10.1001/jamacardio.2016.1829.
Hijazi Z, Hohnloser SH, Andersson U, Alexander JH, Hanna M, Keltai M, Parkhomenko A, López-Sendón JL, Lopes RD, Siegbahn A, Granger CB, Wallentin L. Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation in Relation to Renal Function Over Time: Insights From the ARISTOTLE Randomized Clinical Trial. JAMA Cardiol. 2016 Jul 1;1(4):451-60. doi: 10.1001/jamacardio.2016.1170.
Jaspers Focks J, Brouwer MA, Wojdyla DM, Thomas L, Lopes RD, Washam JB, Lanas F, Xavier D, Husted S, Wallentin L, Alexander JH, Granger CB, Verheugt FW. Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial. BMJ. 2016 Jun 15;353:i2868. doi: 10.1136/bmj.i2868.
Hijazi Z, Oldgren J, Lindbäck 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.
Hijazi Z, Lindbäck J, Alexander JH, Hanna M, Held C, Hylek EM, Lopes RD, Oldgren J, Siegbahn A, Stewart RA, White HD, Granger CB, Wallentin L; ARISTOTLE and STABILITY Investigators. The ABC (age, biomarkers, clinical history) stroke risk score: a biomarker-based risk score for predicting stroke in atrial fibrillation. Eur Heart J. 2016 May 21;37(20):1582-90. doi: 10.1093/eurheartj/ehw054. Epub 2016 Feb 25.
Hijazi Z, Aulin J, Andersson U, Alexander JH, Gersh B, Granger CB, Hanna M, Horowitz J, Hylek EM, Lopes RD, Siegbahn A, Wallentin L; ARISTOTLE Investigators. Biomarkers of inflammation and risk of cardiovascular events in anticoagulated patients with atrial fibrillation. Heart. 2016 Apr;102(7):508-17. doi: 10.1136/heartjnl-2015-308887. Epub 2016 Feb 2.
Rao MP, Halvorsen S, Wojdyla D, Thomas L, Alexander JH, Hylek EM, Hanna M, Bahit MC, Lopes RD, De Caterina R, Erol C, Goto S, Lanas F, Lewis BS, Husted S, Gersh BJ, Wallentin L, Granger CB; Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Steering Committee and Investigators. Blood Pressure Control and Risk of Stroke or Systemic Embolism in Patients With Atrial Fibrillation: Results From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial. J Am Heart Assoc. 2015 Dec 1;4(12). pii: e002015. doi: 10.1161/JAHA.115.002015.
Vinereanu D, Stevens SR, Alexander JH, Al-Khatib SM, Avezum A, Bahit MC, Granger CB, Lopes RD, Halvorsen S, Hanna M, Husted S, Hylek EM, Mărgulescu AD, Wallentin L, Atar D. Clinical outcomes in patients with atrial fibrillation according to sex during anticoagulation with apixaban or warfarin: a secondary analysis of a randomized controlled trial. Eur Heart J. 2015 Dec 7;36(46):3268-75. doi: 10.1093/eurheartj/ehv447. Epub 2015 Sep 14.
Avezum A, Lopes RD, Schulte PJ, Lanas F, Gersh BJ, Hanna M, Pais P, Erol C, Diaz R, Bahit MC, Bartunek J, De Caterina R, Goto S, Ruzyllo W, Zhu J, Granger CB, Alexander JH. Apixaban in Comparison With Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: Findings From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial. Circulation. 2015 Aug 25;132(8):624-32. doi: 10.1161/CIRCULATIONAHA.114.014807. Epub 2015 Jun 23.
Held C, Hylek EM, Alexander JH, Hanna M, Lopes RD, Wojdyla DM, Thomas L, Al-Khalidi H, Alings M, Xavier D, Ansell J, Goto S, Ruzyllo W, Rosenqvist M, Verheugt FW, Zhu J, Granger CB, Wallentin L. Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial. Eur Heart J. 2015 May 21;36(20):1264-72. doi: 10.1093/eurheartj/ehu463. Epub 2014 Dec 12.
Hijazi Z, Siegbahn A, Andersson U, Lindahl B, Granger CB, Alexander JH, Atar D, Gersh BJ, Hanna M, Harjola VP, Horowitz J, Husted S, Hylek EM, Lopes RD, McMurray JJ, Wallentin L. Comparison of cardiac troponins I and T measured with high-sensitivity methods for evaluation of prognosis in atrial fibrillation: an ARISTOTLE substudy. Clin Chem. 2015 Feb;61(2):368-78. doi: 10.1373/clinchem.2014.226936. Epub 2014 Dec 1.
Garcia D, Alexander JH, Wallentin L, Wojdyla DM, Thomas L, Hanna M, Al-Khatib SM, Dorian P, Ansell J, Commerford P, Flaker G, Lanas F, Vinereanu D, Xavier D, Hylek EM, Held C, Verheugt FW, Granger CB, Lopes RD. Management and clinical outcomes in patients treated with apixaban vs warfarin undergoing procedures. Blood. 2014 Dec 11;124(25):3692-8. doi: 10.1182/blood-2014-08-595496. Epub 2014 Oct 15.
Wallentin L, Hijazi Z, Andersson U, Alexander JH, De Caterina R, Hanna M, Horowitz JD, Hylek EM, Lopes RD, Asberg S, Granger CB, Siegbahn A; ARISTOTLE Investigators. Growth differentiation factor 15, a marker of oxidative stress and inflammation, for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. Circulation. 2014 Nov 18;130(21):1847-58. doi: 10.1161/CIRCULATIONAHA.114.011204. Epub 2014 Oct 7.
Hijazi Z, Siegbahn A, Andersson U, Granger CB, Alexander JH, Atar D, Gersh BJ, Mohan P, Harjola VP, Horowitz J, Husted S, Hylek EM, Lopes RD, McMurray JJ, Wallentin L; ARISTOTLE Investigators. High-sensitivity troponin I for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. Circulation. 2014 Feb 11;129(6):625-34. doi: 10.1161/CIRCULATIONAHA.113.006286. Epub 2013 Nov 13.
Flaker G, Lopes RD, Al-Khatib SM, Hermosillo AG, Hohnloser SH, Tinga B, Zhu J, Mohan P, Garcia D, Bartunek J, Vinereanu D, Husted S, Harjola VP, Rosenqvist M, Alexander JH, Granger CB; ARISTOTLE Committees and Investigators. Efficacy and safety of apixaban in patients after cardioversion for atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation). J Am Coll Cardiol. 2014 Mar 25;63(11):1082-7. doi: 10.1016/j.jacc.2013.09.062. Epub 2013 Nov 6.
Hijazi Z, Wallentin L, Siegbahn A, Andersson U, Alexander JH, Atar D, Gersh BJ, Hanna M, Harjola VP, Horowitz JD, Husted S, Hylek EM, Lopes RD, McMurray JJ, Granger CB; ARISTOTLE Investigators. High-sensitivity troponin T and risk stratification in patients with atrial fibrillation during treatment with apixaban or warfarin. J Am Coll Cardiol. 2014 Jan 7-14;63(1):52-61. doi: 10.1016/j.jacc.2013.07.093. Epub 2013 Sep 19.
Alexander JH, Levy E, Lawrence J, Hanna M, Waclawski AP, Wang J, Califf RM, Wallentin L, Granger CB. Documentation of study medication dispensing in a prospective large randomized clinical trial: experiences from the ARISTOTLE Trial. Am Heart J. 2013 Sep;166(3):559-65. doi: 10.1016/j.ahj.2013.05.025. Epub 2013 Aug 15.
Garcia DA, Wallentin L, Lopes RD, Thomas L, Alexander JH, Hylek EM, Ansell J, Hanna M, Lanas F, Flaker G, Commerford P, Xavier D, Vinereanu D, Yang H, Granger CB. Apixaban versus warfarin in patients with atrial fibrillation according to prior warfarin use: results from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial. Am Heart J. 2013 Sep;166(3):549-58. doi: 10.1016/j.ahj.2013.05.016. Epub 2013 Jul 25.
Wallentin L, Lopes RD, Hanna M, Thomas L, Hellkamp A, Nepal S, Hylek EM, Al-Khatib SM, Alexander JH, Alings M, Amerena J, Ansell J, Aylward P, Bartunek J, Commerford P, De Caterina R, Erol C, Harjola VP, Held C, Horowitz JD, Huber K, Husted S, Keltai M, Lanas F, Lisheng L, McMurray JJ, Oh BH, Rosenqvist M, Ruzyllo W, Steg PG, Vinereanu D, Xavier D, Granger CB; Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Investigators. Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation. Circulation. 2013 Jun 4;127(22):2166-76. doi: 10.1161/CIRCULATIONAHA.112.142158. Epub 2013 May 2.
McMurray JJ, Ezekowitz JA, Lewis BS, Gersh BJ, van Diepen S, Amerena J, Bartunek J, Commerford P, Oh BH, Harjola VP, Al-Khatib SM, Hanna M, Alexander JH, Lopes RD, Wojdyla DM, Wallentin L, Granger CB; ARISTOTLE Committees and Investigators. Left ventricular systolic dysfunction, heart failure, and the risk of stroke and systemic embolism in patients with atrial fibrillation: insights from the ARISTOTLE trial. Circ Heart Fail. 2013 May;6(3):451-60. doi: 10.1161/CIRCHEARTFAILURE.112.000143. Epub 2013 Apr 10.
Hijazi Z, Wallentin L, Siegbahn A, Andersson U, Christersson C, Ezekowitz J, Gersh BJ, Hanna M, Hohnloser S, Horowitz J, Huber K, Hylek EM, Lopes RD, McMurray JJ, Granger CB. N-terminal pro-B-type natriuretic peptide for risk assessment in patients with atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation). J Am Coll Cardiol. 2013 Jun 4;61(22):2274-84. doi: 10.1016/j.jacc.2012.11.082. Epub 2013 Apr 3.
Lopes RD, Al-Khatib SM, Wallentin L, Yang H, Ansell J, Bahit MC, De Caterina R, Dorian P, Easton JD, Erol C, Ezekowitz JA, Gersh BJ, Granger CB, Hohnloser SH, Horowitz J, Hylek EM, McMurray JJ, Mohan P, Vinereanu D, Alexander JH. Efficacy and safety of apixaban compared with warfarin according to patient risk of stroke and of bleeding in atrial fibrillation: a secondary analysis of a randomised controlled trial. Lancet. 2012 Nov 17;380(9855):1749-58. doi: 10.1016/S0140-6736(12)60986-6. Epub 2012 Oct 2. Erratum in: Lancet. 2013 Jan 19;381(9862):204.
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00412984     History of Changes
Other Study ID Numbers: CV185-030
First Submitted: December 18, 2006
First Posted: December 19, 2006
Results First Submitted: January 25, 2013
Results First Posted: April 29, 2013
Last Update Posted: November 7, 2013
Last Verified: September 2013

Additional relevant MeSH terms:
Atrial Fibrillation
Atrial Flutter
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Apixaban
Warfarin
Anticoagulants
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action


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