Atrial Fibrillation
Conditions
Brief summary
The purpose of this clinical research study is to determine whether apixaban is more effective than acetylsalicylic acid in the prevention of strokes associated with patients with atrial fibrillation. The safety of this treatment will also be studied.
Detailed description
An optional Long-term Open-label Extension Phase of treatment with apixaban will be provided for qualifying participants following the conclusion of the double-blind phase
Interventions
DRUGApixaban
Tablets, oral, 5 mg (2.5 mg in patients meeting any 2 of the following criteria: 80 years of age and older, weight of 60 kilograms or less, and a serum creatinine level of 1.5 mg/dL or higher), twice daily, up to 156 weeks
DRUGAcetylsalicylic acid
Tablets, oral, 81-324 mg, once daily, up to 156 weeks
Sponsors
Pfizer
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Male and female * Age of 50 years or older * Permanent, paroxysmal, or persistent atrial fibrillation (at screening or within 6 months prior to enrollment) documented by 12-lead electrocardiogram) * At least 1 of the following risk factors for stroke: * Prior stroke or transient ischemic attack * Age of 75 years or older * Arterial hypertension on treatment * Diabetes mellitus * Heart failure (New York Health Authority Class 2 or greater at time of enrollment) * Left ventricular ejection fraction of 35% or less, documented within 6 months of enrollment * Peripheral arterial disease (previous arterial revascularization, limb or foot amputation, or current intermittent claudication with ankle-arm systolic blood pressure ratio \<0.9) * Not currently receiving vitamin K antagonist therapy for 1 of the following reasons: * Previous vitamin K antagonist therapy demonstrated as unsuitable and discontinued * Vitamin K antagonist therapy not previously used but expected unsuitable Key
Exclusion criteria
* Women who are pregnant or breast feeding * Women of child bearing potential who are unwilling to meet the study requirements for pregnancy testing or are unwilling or unable to use an acceptable method to avoid pregnancy * Atrial fibrillation due to reversible causes, such as thyrotoxicosis or pericarditis * Valvular disease requiring surgery * Planned ablation procedure for atrial fibrillation to be performed within 3 months * Conditions other than atrial fibrillation that require chronic anticoagulation (such as, prosthetic mechanical heart valve, venous thromboembolism) * Patients with serious bleeding in the last 6 months or at high risk for bleeding, including but not limited to those with: * Active peptic ulcer disease * Platelet count \<100,000/mm\^3 or hemoglobin \<10g/dL * Recent stroke (within 10 days) * Documented hemorrhagic tendencies or blood dyscrasias * Current alcohol or drug abuse or psychosocial reasons that make study participation impractical * Severe comorbid condition with life expectancy \<1 year * Severe renal insufficiency; any patient with a serum creatinine level \>2.5 mg/dL or a calculated creatinine clearance \<25 mL/min is excluded * Alanine transaminase or aspartate aminotransferase levels \>2 times upper limit of normal (ULN) or a total bilirubin level \>1.5 times ULN (unless an alternative causative factor \[such as Gilbert's syndrome\] is identified) * Allergy or adverse reaction to acetylsalicylic acid * Required treatment with a thienopyridine (clopidogrel or ticlopidine) * Prisoners or participants who are compulsory detained (involuntarily incarcerated) * Use of an investigational drug or device within the past 30 days or prior randomization into an apixaban clinical study * Patients who are compulsorily detained for treatment for a psychiatric or physical illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event Rate of Stroke/Systemic Embolism During the Intended-treatment Period | Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy) | Event rate=percent of participants with an event divided by the total participants in the arm. Intended-treatment period=date of randomization to the efficacy cutoff date, which was to be the date on which at least 226 unrefuted original primary efficacy events occurred (date revised to May 28, 2010 following cessation of study for superior efficacy.) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event Rate for the Composite of Stroke of Any Type, Systemic Embolism, Myocardial Infarction, or Vascular Death During the Double-blind Treatment Period | Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy) | Event rate=percent of participants with an event divided by the total participants in the arm. |
| Event Rate of All-cause Death; Net Clinical Benefit-Composite of Stroke, Systemic Embolism, Myocardial Infarction, Vascular Death, and Major Bleeding; and Vascular Death | Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy) | Event rate=percent of participants with an event divided by the total participants in the arm. |
| Event Rates for Major Bleeding, Major or Clinically Relevant Nonmajor (CNRM) Bleeding, and All Bleeding in the Double-blind Period | First dose of study drug (Day 1) to the earlier of a patient's discontinuation of double-blind study drug or the attainment of at least 226 primary efficacy events up to May 28, 2010 | Event rate=percent of participants with an event divided by the total participants in the arm. |
| Rate of Unrefuted Bleeding From First Dose of Double-blind Study Drug to First Occurence of Unrefuted Bleeding During the Double-blind Treatment Period | Day 1 to first bleeding event up to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy) | Event rate=percent of participants with an event divided by the total participants in the arm. |
| Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome | First dose of study drug (Day 1) to 30 days after last dose of blinded study drug | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. |
| Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | First dose of study drug (Day 1) to 30 days after last dose of blinded study drug | BL=baseline, LLN=lower limit of normal, ULN=upper limit of normal. Hemoglobin (g/dL), low: BL\>2 or value ≤8; hematocrit(%), low: \<0.75\*BL; erythrocytes (\*10\^6 cells/μL), low: \<0.75\*BL; platelet count (\*10\^9 cells/L),low: \<100\*10\^9 cells/L; leukocytes (\*10\^3 cells/μL), low if \<0.8\*BL and BL\<LLN or \<LLN and BL \>ULN or \<0.75\*LLN when BL is missing or LLN ≤BL≤ ULN, high if \>1.2\*BL and BL\>ULN or \>ULN when BL and BL\<LLN or \>1.25\*ULN when BL is missing or LLN≤BL≤ULN; neutrophils (absolute), low: \<1.0\*10\^3 cells/μL; eosinophils (absolute), high: \>0.750\*10\^3 cells/μL; basophils (absolute), high: \>0.4\*10\^3 cells/μL; monocytes (absolute), high: 2\*10\^3 cells/μL; lymphocytes (absolute), low if \<0.75\*10\^3 cells/μL, high if \>7.50\*10\^3 cells/μL; ALP (U/L), high: 2\*ULN; AST (U/L), high: 3\*ULN; AST (U/L), high: 3\*ULN; bilirubin, total (mg/dL), high: \>2\*ULN; bilirubin, direct (mg/dL), high: 1.5\*ULN; BUN (mg/dL), high:\>2\*ULN; creatinine (mg/dL), high: \>1.5\*ULN. |
| Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | First dose of study drug (Day 1) to 30 days after last dose of blinded study drug | LLN=lower limit of normal; ULN=upper limit of normal; BL=baseline. Sodium, serum (mEq/L):low if \<0.95\*BL and BL\<LLN or \<LLN and BL\>ULN or \<0.95\*LLN when BL missing or LLN ≤BL≤ULN, high if \>1.05\*BL and BL\>ULN or \>ULN and BL\<LLN or \>1.05\*ULN when BL missing or LLN≤BL≤ULN; potassium(mEq/L):low if \<0.90\*BL and BL\<LLN or \<LLN and BL\>ULN or \<0.90\*LLN if BL missing or LLN≤BL≤ULN, high if \>1.10\*BL and BL\>ULN or\>ULN and BL\<LLN or \>1.10\*ULN when BL missing or LLN≤BL≤ULN; chloride(mEq/L):low if \<0.90\*BL and BL\<LLN or \<LLN and BL\>ULN or \<0.90\*LLN if BL missing or LLN≤BL ≤ULN, high if \>1.10\*BL and BL\>ULN or \>ULN and BL\<LLN or \>1.10\* ULN if BL missing or LLN≤BL≤ULN; calcium(mg/dL):low if \<0.75\*BL and BL\<LLN or \<LLN and BL\>ULN or \<0.80\*LLN if BL missing or LLN≤BL≤ULN, high if \>1.25\*BL and BL\>ULN or \>ULN if BL\<LLN or \>1.20\*ULN if BL missing or LLN≤BL≤ULN ; bicarbonate(mEq/L):low if \<0.75\*BL when BL\<LLN or \<LLN when BL\>ULN or \<0.75\*LLN if BL missing or LLN≤BL≤ULN, high if \>1.25\*BL when BL\>ULN or \>ULN |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Czechia, Denmark, Finland, France, Germany, Greece, Hong Kong, India, Indonesia, Israel, Italy, Malaysia, Mexico, Norway, Philippines, Poland, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
A total 6421 patients were enrolled in the study. Of these, 5598 were randomized (2807 to apixaban and 2791 to acetylsalicylic acid). Most (435) of the patients who were not randomized (823) no longer met study criteria. Of those randomized, 5578 received treatment (2798 with apixaban, and 2780 with acetylsalicylic acid).
Participants by arm
| Arm | Count |
|---|---|
| Apixaban, 2.5 or 5 mg Twice Daily Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria. | 2,807 |
| Acetylsalicylic Acid, 81-324 mg Once Daily Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion | 2,791 |
| Total | 5,598 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double Blind | >=1 reason assigned per patient | 558 | 649 | 0 |
| Open Label | >=1 reason assigned per patient | 0 | 0 | 1,011 |
Baseline characteristics
| Characteristic | Apixaban, 2.5 or 5 mg Twice Daily | Acetylsalicylic Acid, 81-324 mg Once Daily | Total |
|---|---|---|---|
| Age, Continuous | 69.7 years STANDARD_DEVIATION 9.44 | 70.0 years STANDARD_DEVIATION 9.71 | 69.9 years STANDARD_DEVIATION 9.58 |
| Age, Customized >=65 but <75 years | 1049 Participants | 938 Participants | 1987 Participants |
| Age, Customized < 65 years | 855 Participants | 865 Participants | 1720 Participants |
| Age, Customized >=75 years | 903 Participants | 988 Participants | 1891 Participants |
| Number of Participants by Number of Risk Factors for Stroke 1 or fewer | 1085 Participants | 1077 Participants | 2162 Participants |
| Number of Participants by Number of Risk Factors for Stroke 2 or more | 1722 Participants | 1714 Participants | 3436 Participants |
| Number of Participants With Risk Factors for Stroke Age of 75 years or older | 903 Participants | 988 Participants | 1891 Participants |
| Number of Participants With Risk Factors for Stroke Diabetes mellitus | 536 Participants | 559 Participants | 1095 Participants |
| Number of Participants With Risk Factors for Stroke Heart failure (NYHA class ≥2) or LVEF ≤35% | 961 Participants | 926 Participants | 1887 Participants |
| Number of Participants With Risk Factors for Stroke Hypertension requiring pharmacologic treatment | 2408 Participants | 2429 Participants | 4837 Participants |
| Number of Participants With Risk Factors for Stroke Peripheral artery disease | 66 Participants | 78 Participants | 144 Participants |
| Number of Participants With Risk Factors for Stroke Prior stroke or transient ischemic attack | 390 Participants | 374 Participants | 764 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 6 Participants | 6 Participants | 12 Participants |
| Race/Ethnicity, Customized Asian | 541 Participants | 544 Participants | 1085 Participants |
| Race/Ethnicity, Customized Black or African American | 10 Participants | 26 Participants | 36 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Other | 26 Participants | 36 Participants | 62 Participants |
| Race/Ethnicity, Customized White | 2221 Participants | 2178 Participants | 4399 Participants |
| Sex: Female, Male Female | 1147 Participants | 1174 Participants | 2321 Participants |
| Sex: Female, Male Male | 1660 Participants | 1617 Participants | 3277 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 111 / 2,798 | 140 / 2,780 | 286 / 3,275 |
| other Total, other adverse events | 207 / 2,798 | 267 / 2,780 | 180 / 3,275 |
| serious Total, serious adverse events | 657 / 2,798 | 804 / 2,780 | 1,228 / 3,275 |
Outcome results
Primary
Event Rate of Stroke/Systemic Embolism During the Intended-treatment Period
Event rate=percent of participants with an event divided by the total participants in the arm. Intended-treatment period=date of randomization to the efficacy cutoff date, which was to be the date on which at least 226 unrefuted original primary efficacy events occurred (date revised to May 28, 2010 following cessation of study for superior efficacy.)
Time frame: Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban, 2.5 or 5 mg Twice Daily | Event Rate of Stroke/Systemic Embolism During the Intended-treatment Period | 1.62 Percentage of events |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Event Rate of Stroke/Systemic Embolism During the Intended-treatment Period | 3.63 Percentage of events |
p-value: <0.0000195% CI: [0.32, 0.62]Log Rank
Secondary
Event Rate for the Composite of Stroke of Any Type, Systemic Embolism, Myocardial Infarction, or Vascular Death During the Double-blind Treatment Period
Event rate=percent of participants with an event divided by the total participants in the arm.
Time frame: Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban, 2.5 or 5 mg Twice Daily | Event Rate for the Composite of Stroke of Any Type, Systemic Embolism, Myocardial Infarction, or Vascular Death During the Double-blind Treatment Period | 4.21 Percentage of events per year |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Event Rate for the Composite of Stroke of Any Type, Systemic Embolism, Myocardial Infarction, or Vascular Death During the Double-blind Treatment Period | 6.35 Percentage of events per year |
p-value: 0.0002695% CI: [0.53, 0.83]Log Rank
Secondary
Event Rate of All-cause Death; Net Clinical Benefit-Composite of Stroke, Systemic Embolism, Myocardial Infarction, Vascular Death, and Major Bleeding; and Vascular Death
Event rate=percent of participants with an event divided by the total participants in the arm.
Time frame: Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban, 2.5 or 5 mg Twice Daily | Event Rate of All-cause Death; Net Clinical Benefit-Composite of Stroke, Systemic Embolism, Myocardial Infarction, Vascular Death, and Major Bleeding; and Vascular Death | All-cause death (n=111, 140) | 3.51 Percentage of events per year |
| Apixaban, 2.5 or 5 mg Twice Daily | Event Rate of All-cause Death; Net Clinical Benefit-Composite of Stroke, Systemic Embolism, Myocardial Infarction, Vascular Death, and Major Bleeding; and Vascular Death | Net clinical benefit (n=163, 220) | 5.23 Percentage of events per year |
| Apixaban, 2.5 or 5 mg Twice Daily | Event Rate of All-cause Death; Net Clinical Benefit-Composite of Stroke, Systemic Embolism, Myocardial Infarction, Vascular Death, and Major Bleeding; and Vascular Death | Vascular death (n=84, 96) | 2.65 Percentage of events per year |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Event Rate of All-cause Death; Net Clinical Benefit-Composite of Stroke, Systemic Embolism, Myocardial Infarction, Vascular Death, and Major Bleeding; and Vascular Death | All-cause death (n=111, 140) | 4.42 Percentage of events per year |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Event Rate of All-cause Death; Net Clinical Benefit-Composite of Stroke, Systemic Embolism, Myocardial Infarction, Vascular Death, and Major Bleeding; and Vascular Death | Net clinical benefit (n=163, 220) | 7.13 Percentage of events per year |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Event Rate of All-cause Death; Net Clinical Benefit-Composite of Stroke, Systemic Embolism, Myocardial Infarction, Vascular Death, and Major Bleeding; and Vascular Death | Vascular death (n=84, 96) | 3.03 Percentage of events per year |
p-value: 0.0678295% CI: [0.62, 1.02]Log Rank
p-value: 0.002895% CI: [0.6, 0.9]Log Rank
p-value: 0.3658695% CI: [0.65, 1.17]Log Rank
Secondary
Event Rates for Major Bleeding, Major or Clinically Relevant Nonmajor (CNRM) Bleeding, and All Bleeding in the Double-blind Period
Event rate=percent of participants with an event divided by the total participants in the arm.
Time frame: First dose of study drug (Day 1) to the earlier of a patient's discontinuation of double-blind study drug or the attainment of at least 226 primary efficacy events up to May 28, 2010
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban, 2.5 or 5 mg Twice Daily | Event Rates for Major Bleeding, Major or Clinically Relevant Nonmajor (CNRM) Bleeding, and All Bleeding in the Double-blind Period | Major bleeding | 1.41 Percentage of events per year |
| Apixaban, 2.5 or 5 mg Twice Daily | Event Rates for Major Bleeding, Major or Clinically Relevant Nonmajor (CNRM) Bleeding, and All Bleeding in the Double-blind Period | Major or CRNM bleeding | 4.46 Percentage of events per year |
| Apixaban, 2.5 or 5 mg Twice Daily | Event Rates for Major Bleeding, Major or Clinically Relevant Nonmajor (CNRM) Bleeding, and All Bleeding in the Double-blind Period | All bleeding | 10.85 Percentage of events per year |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Event Rates for Major Bleeding, Major or Clinically Relevant Nonmajor (CNRM) Bleeding, and All Bleeding in the Double-blind Period | Major bleeding | 0.92 Percentage of events per year |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Event Rates for Major Bleeding, Major or Clinically Relevant Nonmajor (CNRM) Bleeding, and All Bleeding in the Double-blind Period | Major or CRNM bleeding | 3.24 Percentage of events per year |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Event Rates for Major Bleeding, Major or Clinically Relevant Nonmajor (CNRM) Bleeding, and All Bleeding in the Double-blind Period | All bleeding | 8.32 Percentage of events per year |
p-value: 0.071695% CI: [0.96, 2.45]Log Rank
p-value: 0.001795% CI: [1.1, 1.53]Log Rank
p-value: 0.014495% CI: [1.07, 1.78]Log Rank
Secondary
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality
BL=baseline, LLN=lower limit of normal, ULN=upper limit of normal. Hemoglobin (g/dL), low: BL\>2 or value ≤8; hematocrit(%), low: \<0.75\*BL; erythrocytes (\*10\^6 cells/μL), low: \<0.75\*BL; platelet count (\*10\^9 cells/L),low: \<100\*10\^9 cells/L; leukocytes (\*10\^3 cells/μL), low if \<0.8\*BL and BL\<LLN or \<LLN and BL \>ULN or \<0.75\*LLN when BL is missing or LLN ≤BL≤ ULN, high if \>1.2\*BL and BL\>ULN or \>ULN when BL and BL\<LLN or \>1.25\*ULN when BL is missing or LLN≤BL≤ULN; neutrophils (absolute), low: \<1.0\*10\^3 cells/μL; eosinophils (absolute), high: \>0.750\*10\^3 cells/μL; basophils (absolute), high: \>0.4\*10\^3 cells/μL; monocytes (absolute), high: 2\*10\^3 cells/μL; lymphocytes (absolute), low if \<0.75\*10\^3 cells/μL, high if \>7.50\*10\^3 cells/μL; ALP (U/L), high: 2\*ULN; AST (U/L), high: 3\*ULN; AST (U/L), high: 3\*ULN; bilirubin, total (mg/dL), high: \>2\*ULN; bilirubin, direct (mg/dL), high: 1.5\*ULN; BUN (mg/dL), high:\>2\*ULN; creatinine (mg/dL), high: \>1.5\*ULN.
Time frame: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug
Population: Participants who received at least 1 dose of study drug. n=number evaluable
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Leukocytes, low (n=1738, 1698) | 12 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Hemoglobin, high (n=1956, 1893) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Hematocrit, low (n=1728, 1687) | 13 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Hematocrit, high (n=1728, 1687) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Erythrocytes, low (n=1728, 1687) | 12 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Erythrocytes, high (n=1728, 1687) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Platelet count, low (n=2148, 2098) | 7 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Platelet count, high (n=2148, 2098) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Hemoglobin, low (n=1956, 1893) | 131 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Leukocytes, high (n=1738, 1698) | 14 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Neutrophils (absolute), low (n=2170, 2138) | 2 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Neutrophils (absolute), high (n=2170, 2138) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Eosinophils (absolute), low (n=2170, 2138) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Eosinophils (absolute), high (n=2170, 2138) | 48 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Basophils (absolute), low (n=2170, 2138) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Basophils (absolute), high (n=2170, 2138) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Monocytes (absolute), low (n=2170, 2138) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Monocytes (absolute), high (n=2170, 2138) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Lymphocytes (absolute), low (n=2170, 2138) | 52 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Lymphocytes (absolute), high (n=2170, 2138) | 4 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Alkaline phosphatase (ALP), low (n=2781, 2758) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | ALP, high (n=2781, 2758) | 34 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Aspartate phosphatase (AST), low (n=2779, 2753) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | AST, high (n=2779, 2753) | 28 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Alanine aminotransferase (ALT), low (n=2779, 2753) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | ALT, high (n=2779, 2753) | 23 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Bilirubin (total), low (n=2781, 2758) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Bilirubin (total), high (n=2781, 2758) | 30 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Bilirubin (direct), low (n=2773, 2750) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Bilirubin (direct), high (n=2773, 2750) | 241 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Blood urea nitrogen (BUN), low (n=2201, 2172) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | BUN, high (n=2201, 2172) | 42 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Creatinine, low (n=2209, 2178) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Creatinine, high (n=2209, 2178) | 67 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | ALT, high (n=2779, 2753) | 31 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Hemoglobin, low (n=1956, 1893) | 120 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Monocytes (absolute), high (n=2170, 2138) | 2 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Hemoglobin, high (n=1956, 1893) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Creatinine, high (n=2209, 2178) | 71 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Hematocrit, low (n=1728, 1687) | 9 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Lymphocytes (absolute), low (n=2170, 2138) | 62 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Hematocrit, high (n=1728, 1687) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Bilirubin (total), low (n=2781, 2758) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Erythrocytes, low (n=1728, 1687) | 12 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Lymphocytes (absolute), high (n=2170, 2138) | 5 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Erythrocytes, high (n=1728, 1687) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | BUN, high (n=2201, 2172) | 50 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Platelet count, low (n=2148, 2098) | 10 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Alkaline phosphatase (ALP), low (n=2781, 2758) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Platelet count, high (n=2148, 2098) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Bilirubin (total), high (n=2781, 2758) | 43 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Leukocytes, low (n=1738, 1698) | 14 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | ALP, high (n=2781, 2758) | 27 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Leukocytes, high (n=1738, 1698) | 18 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Blood urea nitrogen (BUN), low (n=2201, 2172) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Neutrophils (absolute), low (n=2170, 2138) | 1 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Aspartate phosphatase (AST), low (n=2779, 2753) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Neutrophils (absolute), high (n=2170, 2138) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Bilirubin (direct), low (n=2773, 2750) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Eosinophils (absolute), low (n=2170, 2138) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | AST, high (n=2779, 2753) | 33 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Eosinophils (absolute), high (n=2170, 2138) | 68 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Creatinine, low (n=2209, 2178) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Basophils (absolute), low (n=2170, 2138) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Alanine aminotransferase (ALT), low (n=2779, 2753) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Basophils (absolute), high (n=2170, 2138) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Bilirubin (direct), high (n=2773, 2750) | 248 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality | Monocytes (absolute), low (n=2170, 2138) | 0 Participants |
Secondary
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued)
ULN=upper limit of normal; LLN=lower limit of normal; BL=baseline. Creatine kinase (U/L), high:\>5\*ULN; protein, total(g/L):low if \<0.90\*BL when BL\<LLN or \<LLN when B \>ULN or \<0.90\*LLN when BL is missing or LLN≤BL≤ULN, high if \>1.10\*BL if BL\>ULN or \>ULN when BL\<LLN or \>1.10\*ULN if BL missing or LLN≤BL≤ULN.Protein,total(g/L): low if \<0.90\*BL if BL\<LLN or \<LLN if BL\>ULN or \<0.90\*LLN if BL missing or LLN≤BL≤ULN, high if \>1.10\*BL if BL\>ULN or \>ULN if BL\<LLN or \>1.10\*ULN if BL or LLN≤BL≤ULN; glucose, serum fasting (mg/dL): low if \<0.8\*BL if BL\<LLN or \<LLN when BL\>ULN or \<0.8\*LLN when BL missing or LLN≤BL≤ULN, high if \>2\*BL when BL\>ULN or \>ULN when BL\<LLN or \>1.5\*ULN if BL missing or LLN≤BL≤ULN; uric acid (mg/dL), high: \>2\*BL and BL\>ULN or\>1.5\*ULN when BL missing or BL≤ULN; glucose, urine, high; protein, urine, high; blood, urine, high; leukocyte esterase, urine, high; RBC count, urine (Hpf), high; WBC count, urine (Hpf), high: ≥2 if BL=missing,=0 or =0.5 or if ≥3 if BL=1, or if ≥4 and BL≥2.
Time frame: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug
Population: Participants who received at least 1 dose of study drug. n=number evaluable
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Leukocyte esterase (urine), low (n=3,5) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Leukocyte esterase (urine), high (n=3,5) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Red blood cells (RBC) (urine), low (n=2,2) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | RBC (urine), high (n=2,2) | 1 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | White blood cells (urine), low (n=2,2) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | WBC (urine), high (n=2,2) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Creatine kinase, low (n=2780, 2758) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Creatine kinase, high (n=2780, 2758) | 13 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Protein (total), low (n=103, 109) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Protein (total), high (n=103, 109) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Uric acid, low (n=386, 390) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Uric acid, high (n=386, 390) | 1 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Glucose (urine), low (n=2, 3) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Glucose (urine), high (n=2, 3) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Protein (urine), low (n=3, 5) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Protein (urine), high (n=3, 5) | 1 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Blood (urine), low (n=3, 5) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Blood (urine), high (n=3, 5) | 1 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Glucose (urine), high (n=2, 3) | 1 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Leukocyte esterase (urine), low (n=3,5) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Red blood cells (RBC) (urine), low (n=2,2) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Protein (total), high (n=103, 109) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Leukocyte esterase (urine), high (n=3,5) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Blood (urine), high (n=3, 5) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Uric acid, low (n=386, 390) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | RBC (urine), high (n=2,2) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Protein (urine), low (n=3, 5) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | White blood cells (urine), low (n=2,2) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Uric acid, high (n=386, 390) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | WBC (urine), high (n=2,2) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Blood (urine), low (n=3, 5) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Creatine kinase, low (n=2780, 2758) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Glucose (urine), low (n=2, 3) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Creatine kinase, high (n=2780, 2758) | 25 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Protein (urine), high (n=3, 5) | 1 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Protein (total), low (n=103, 109) | 0 Participants |
Secondary
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued)
LLN=lower limit of normal; ULN=upper limit of normal; BL=baseline. Sodium, serum (mEq/L):low if \<0.95\*BL and BL\<LLN or \<LLN and BL\>ULN or \<0.95\*LLN when BL missing or LLN ≤BL≤ULN, high if \>1.05\*BL and BL\>ULN or \>ULN and BL\<LLN or \>1.05\*ULN when BL missing or LLN≤BL≤ULN; potassium(mEq/L):low if \<0.90\*BL and BL\<LLN or \<LLN and BL\>ULN or \<0.90\*LLN if BL missing or LLN≤BL≤ULN, high if \>1.10\*BL and BL\>ULN or\>ULN and BL\<LLN or \>1.10\*ULN when BL missing or LLN≤BL≤ULN; chloride(mEq/L):low if \<0.90\*BL and BL\<LLN or \<LLN and BL\>ULN or \<0.90\*LLN if BL missing or LLN≤BL ≤ULN, high if \>1.10\*BL and BL\>ULN or \>ULN and BL\<LLN or \>1.10\* ULN if BL missing or LLN≤BL≤ULN; calcium(mg/dL):low if \<0.75\*BL and BL\<LLN or \<LLN and BL\>ULN or \<0.80\*LLN if BL missing or LLN≤BL≤ULN, high if \>1.25\*BL and BL\>ULN or \>ULN if BL\<LLN or \>1.20\*ULN if BL missing or LLN≤BL≤ULN ; bicarbonate(mEq/L):low if \<0.75\*BL when BL\<LLN or \<LLN when BL\>ULN or \<0.75\*LLN if BL missing or LLN≤BL≤ULN, high if \>1.25\*BL when BL\>ULN or \>ULN
Time frame: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug
Population: Participants who received at least 1 dose of study drug. n=number evaluable
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Sodium (serum), low (n=1768, 1740) | 2 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Sodium (serum), high (n=1768, 1740) | 1 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Potassium (serum), low (n=1763, 1737) | 6 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Potassium (serum), high (n=1763, 1737) | 20 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Chloride (serum), low (n=1768, 1740) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Chloride (serum), high (n=1768, 1740) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Calcium (total), low (n=106, 109) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Calcium (total), high (n=106, 109) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Bicarbonate, low (n=1664, 1619) | 0 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Bicarbonate, high (n=1664, 1619) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Calcium (total), high (n=106, 109) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Sodium (serum), low (n=1768, 1740) | 6 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Chloride (serum), high (n=1768, 1740) | 1 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Sodium (serum), high (n=1768, 1740) | 2 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Bicarbonate, high (n=1664, 1619) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Potassium (serum), low (n=1763, 1737) | 8 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Calcium (total), low (n=106, 109) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Potassium (serum), high (n=1763, 1737) | 28 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Bicarbonate, low (n=1664, 1619) | 0 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) | Chloride (serum), low (n=1768, 1740) | 3 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Time frame: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome | SAEs | 657 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome | Discontinuations due to AE | 266 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome | Bleeding AEs | 281 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome | Deaths | 91 Participants |
| Apixaban, 2.5 or 5 mg Twice Daily | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome | AEs | 1833 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome | Deaths | 115 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome | AEs | 1925 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome | SAEs | 804 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome | Bleeding AEs | 259 Participants |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome | Discontinuations due to AE | 362 Participants |
Secondary
Rate of Unrefuted Bleeding From First Dose of Double-blind Study Drug to First Occurence of Unrefuted Bleeding During the Double-blind Treatment Period
Event rate=percent of participants with an event divided by the total participants in the arm.
Time frame: Day 1 to first bleeding event up to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban, 2.5 or 5 mg Twice Daily | Rate of Unrefuted Bleeding From First Dose of Double-blind Study Drug to First Occurence of Unrefuted Bleeding During the Double-blind Treatment Period | 10.85 Percentage of events per year |
| Acetylsalicylic Acid, 81-324 mg Once Daily | Rate of Unrefuted Bleeding From First Dose of Double-blind Study Drug to First Occurence of Unrefuted Bleeding During the Double-blind Treatment Period | 8.32 Percentage of events per year |
p-value: 0.001795% CI: [1.1, 1.53]Log Rank