None listed
Conditions
Interventions
Group 1 Type of group
Two initial daily doses of up to 6 mg of warfarin orally, dose adjusted for an INR target of 2.0 - 3.0 or similar placebo for the treatment period.
Group name:Group 2 Type of group
Tablets of 5 mg or 2.5 mg of oral apixaban administered twice a day or similar placebo for the treatment period (average of 1.8 years of follow-up since randomization)
Sponsors
BRISTOL MYERS SQUIBB COMPANY,
Eligibility
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: • Age> 18 years • In atrial fibrillation or atrial flutter not due to reversible cause and documented by ECG at the time of enrollment • One or more of the following risk factors for stroke: Age 75 years of age or older, stroke, TIA or previous systemic embolism, c) Symptomatic congestive heart failure within 3 months or left ventricular dysfunction with a fraction of LV ejection (LVEF) <40% as measured by echocardiography, study with radionucleotides or contrast angiography, Diabetes mellitus, Hypertension requiring pharmacological treatment • Women of childbearing age should use adequate contraception to avoid pregnancy during the study treatment period or for 2 weeks after the last dose of study medication, whichever is longer, in order to minimize the risk of pregnancy . • All subjects must provide signed written informed consent.
Exclusion criteria
Exclusion criteria: • Fibrillation or atrial flutter due to reversible causes (eg thyrotoxicosis, pericarditis) • Clinically significant mitral stenosis (moderate or severe) • Risk of increased bleeding believed to be a contraindication to oral anticoagulation (eg, previous intracranial hemorrhage) • Conditions other than atrial fibrillation requiring chronic anticoagulation (eg mechanical prosthetic heart valve) • Persistent uncontrolled hypertension (systolic BP> 180 mmHg, or diastolic BP> 100 mmHg) • Active infectious endocarditis • Major surgery planning • Procedure planning for fibrillation or atrial flutter ablation • Use of a medication or experimental device not approved within the last 30 days • Requires treatment with> 165 mg / day of aspirin • Simultaneous treatment with aspirin and a thienopyridine (eg clopidogrel, ticlopidine) • Severe comorbid condition with life expectancy 2.5 mg / dl or calculated creatinine clearance 2 x ULN or a total bilirubin> 1.5 x ULN (unless an alternative causative factor is identified [eg, Gilbert´s syndrome]) • Platelet count <100,000 / mm3 • Hemoglobin <9 g / dl • Inability to comply with INR monitoring • Prior randomization in a clinical study with apixaban • Prisoners or subjects with involuntary imprisonment • Subjects compulsorily detained for the treatment of a psychiatric or physical illness (eg, infectious disease). • Women of childbearing age unable or unwilling to use an acceptable contraceptive method to avoid pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name: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. Measure:Number of Participants With First Event of Ischemic/Unspecified Stroke, Hemorrhagic Stroke, or Systemic Embolism (SE) During the Intended Treatment Period Timepoints:Time to first event in Intended Treatment Period: started on day of randomization, ended at efficacy cut-off date ; Outcome name: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. Measure:Rate of Adjudicated Stroke or Systemic Embolism (SE) During the Intended Treatment Period Timepoints:Intended Treatment Period started on the day of randomization and ended at the efficacy cut-off date | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name: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 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. Measure:Number of Participants With Event of Major (International Society on Thrombosis and Hemostasis [ISTH]) Bleeding During Treatment Period Timepoints: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 ; Outcome name: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. Measure:Rate of Adjudicated Major (ISTH) Bleed Events During Treatment Period Timepoints: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. ; Outcome name:Death was defined as all-cause mortality. All unobserved deaths were assumed to be cardiovascular in nature unless a non-car | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Czech Republic, Denmark, Finland, France, Germany, Hungary, India, Israel, Italy, Japan, Korea South, Malasya, Mexico, Netherlands, Norway, Philippines, Poland, Romania, Russian Federation, Singapore, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kindgdom, United States
Outcome results
None listed