Acute Coronary Syndrome (ACS)
Conditions
Brief summary
The purpose of this clinical research study is to determine whether apixaban will be safe in people who have recently had unstable angina or a heart attack.
Interventions
DRUGApixaban
Tablets, Oral, 2.5 mg, twice daily, 26 weeks
DRUGPlacebo
Tablets, Oral, 0, twice daily, 26 weeks
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Recent (\< = 7 days) Acute Coronary Syndrome (ACS). * Clinically stable on optimal treatment Key
Exclusion criteria
* High bleeding risk. * Ongoing anticoagulant use. * Need for chronic (\>3 months) daily nonsteroidal anti-inflammatory drug (NSAID) or chronic high dose acetylsalicylic acid (ASA) use (\>325 mg/day
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Treatment Period- Treated Participants With Placebo or Apixaban Low Doses | From first dose of study drug (Day 1) to last dose plus 2 days, up to Year 2 of the Study | Bleeding was assessed using the International Society on Thrombosis and Hemostasis (ISTH) guidelines. Events were adjudicated by the Clinical Events Committee (CEC). Event rate was number of participants with events divided by the number of participants treated, measured as a percentage (%). The primary outcome is based on data for the placebo and 2 apixaban low-dose groups (2.5 mg BID and 10 mg QD) combined across Phase A and Phase B. The analyses of Phase B data across all doses of apixaban are secondary because of the premature termination of the apixaban high-dose groups (10mg BID, 20mg QD) and the resulting lower duration of exposure for these groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event Rate for Adjudicated All Bleeding Events During the Treatment Period - Treated Participants With Placebo or Apixaban Low Doses | first dose (Day 1) to last dose plus 2 days (or for SAEs, plus 30 days), up to Year 2 of the Study | Bleeding was assessed using the International Society on Thrombosis and Hemostasis (ISTH) guidelines. Events were adjudicated by the Clinical Events Committee (CEC). Event rate was number of participants with events divided by the number of participants treated (%). All bleeding events includes major bleeding, clinically relevant non-major bleeding and minor bleeding. Treatment Period refers to the period from first dose through 2 days, or through 30 days for Serious Adverse Event (SAE) tabulations, after discontinuation of study drug. Data in this outcome are combined across Phase A and Phase B. |
| Number of Participants With a Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, and Non-Hemorrhagic Stroke During the Intended Treatment Period - Randomized Participants | Day of randomization to 182 days after day of randomization (183 days) | Events were adjudicated by the Clinical Events Committee (CEC). Event rate was number of participants with events divided by the number of participants treated (%). Intended Treatment Period refers to the period starting on the day of randomization and ending 182 days after the day of randomization (for a total period duration of 183 days). Data in this outcome are combined across Phase A and Phase B |
| Event Rate of Confirmed Adjudicated Major Bleeding During the Treatment Period- Treated Participants With Placebo or Apixaban Low Doses | from first dose (Day 1) to last dose plus 2 days, up to Year 2 of the Study | Bleeding was assessed using the ISTH guidelines. Events were adjudicated by the Clinical Events Committee. Event rate was number of participants with events divided by the number of participants treated, measured as a percentage (%). |
| Number of Participants With Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B | Day of randomization and ends on high dose termination date, 1-Oct-2007 | Phase B Adjusted Intended Treatment Period=day of randomization and ends on termination date of high dose apixaban, 1-Oct-2007. The analyses of Phase B data across all doses of apixaban are secondary due to the premature termination of the apixaban high dose groups and the lower duration of exposure. |
| Number of Participants With a Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia and Non-Hemorrhagic Stroke During the Intended Treatment Period - Randomized Participants | Randomization to 182 days after randomization (183 days) | Events were adjudicated by the Clinical Events Committee (CEC). Intended Treatment Period refers to the period starting on the day of randomization and ending 182 days after the day of randomization (for a total period duration of 183 days). Data in this outcome are combined across Phase A and Phase B. |
| Event Rate for Adjudicated All Bleeding Events During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B | From first dose (Day 1) to last dose, plus 2 days (plus 30 days for SAEs), up to high dose termination, 1 October 2007 | Bleeding was assessed using the ISTH guidelines. Events were adjudicated by the CEC. Event rate was number of participants with events divided by the number of participants treated (%). All bleeding events included major bleeding, clinically relevant non-major bleeding and minor bleeding. Phase B Adjusted Treatment Period=safety events occurring in the period from first dose through 2 days (or through 30 days for SAE tabulations) after the earliest of last dose date or 1-Oct-2007 (termination date for the 10 mg BID group). |
| Number of Participants With Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B | Day of randomization up to high dose termination, 1-Oct-2007 | Phase B Adjusted Intended Treatment Period=day of randomization and ends on 1-Oct-2007. The analyses of Phase B data across all doses of apixaban are secondary due to the premature termination of the apixaban high dose groups and the lower duration of exposure. |
| Event Rate of Confirmed Adjudicated Major Bleeding During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B | From first dose (Day 1) to last dose, plus 2 days (plus 30 days for SAEs), up to high dose termination, 1 October 2007 | Bleeding was assessed using the ISTH guidelines. Events were adjudicated by the CEC. Event rate was number of participants with events divided by the number of participants treated (%). |
| Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Phase B Adjusted Treatment Period- Treated Participants Randomized in Phase B | From first dose (Day 1) to last dose, plus 2 days (plus 30 days for SAEs), up to high dose termination, 1 October 2007 | Bleeding was assessed using ISTH guidelines. Events were adjudicated by the CEC. Event rate was number of participants with events divided by the number of participants treated, measured as a percentage (%). The analyses of Phase B data across all doses of apixaban are secondary because of the premature termination of the apixaban high-dose groups and the lower duration of exposure. Phase B Adjusted Treatment Period=safety events occurring in the period from first dose through 2 days (or through 30 days for SAE tabulations) after the earliest of last dose date or 1-Oct-2007 (termination date for the 10 mg BID group). |
Countries
Austria, Belgium, Canada, Denmark, France, Germany, Israel, Italy, Poland, Russia, Spain, Sweden, United Kingdom, United States
Participant flow
Pre-assignment details
1741 enrolled; 1715 randomized. Non-randomization reasons: 6 withdrew consent, 1 death, 1 poor/non-compliance, 18 no longer met study criteria. Phase A: placebo and 2 low doses of apixaban; Phase B: placebo, 2 low doses and 2 high doses of apixaban. High dose arms terminated, Phase B continued to enroll participants into placebo and low dose arms.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Tablet of Placebo for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. | 611 |
| Apixaban 2.5mg BID Tablet of Apixaban 2.5mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. | 317 |
| Apixaban 10mg QD Tablet of Apixaban 10mg QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. | 318 |
| Apixaban 10mg BID Tablet of Apixaban 10mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion.
Approximately 6 months after the start of Phase B, this treatment group was terminated | 248 |
| Apixaban 20 mg QD Tablet of apixaban, oral, for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion.
Approximately 6 months after the start of Phase B, this treatment group was terminated. | 221 |
| Total | 1,715 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Follow-Up(30days)-Randomized Phase A | Death | 0 | 1 | 0 | 0 | 0 |
| Follow-Up(30days)-Randomized Phase A | Withdrawal by Subject | 5 | 5 | 2 | 0 | 0 |
| Follow-Up(30days)-Randomized Phase B | Death | 1 | 0 | 0 | 0 | 0 |
| Follow-Up(30days)-Randomized Phase B | Lost to Follow-up | 0 | 0 | 0 | 2 | 1 |
| Follow-Up(30days)-Randomized Phase B | missing end of study status | 1 | 0 | 0 | 2 | 0 |
| Follow-Up(30days)-Randomized Phase B | Withdrawal by Subject | 1 | 0 | 2 | 1 | 1 |
| Randomized in Phase A (26 Weeks) | Administrative reason (arm terminated) | 1 | 0 | 0 | 0 | 0 |
| Randomized in Phase A (26 Weeks) | Adverse Event | 19 | 14 | 17 | 0 | 0 |
| Randomized in Phase A (26 Weeks) | Death | 3 | 4 | 0 | 0 | 0 |
| Randomized in Phase A (26 Weeks) | Lost to Follow-up | 4 | 4 | 2 | 0 | 0 |
| Randomized in Phase A (26 Weeks) | no longer meets criteria | 4 | 3 | 2 | 0 | 0 |
| Randomized in Phase A (26 Weeks) | Poor/non-compliance | 3 | 2 | 1 | 0 | 0 |
| Randomized in Phase A (26 Weeks) | Withdrawal by Subject | 20 | 12 | 13 | 0 | 0 |
| Randomized in Phase B (26 Weeks) | Administrative reason by Sponsor | 2 | 1 | 0 | 193 | 164 |
| Randomized in Phase B (26 Weeks) | Adverse Event | 34 | 9 | 12 | 23 | 19 |
| Randomized in Phase B (26 Weeks) | Death | 5 | 3 | 1 | 0 | 1 |
| Randomized in Phase B (26 Weeks) | Lost to Follow-up | 5 | 2 | 3 | 2 | 3 |
| Randomized in Phase B (26 Weeks) | no longer meets criteria | 9 | 3 | 2 | 0 | 2 |
| Randomized in Phase B (26 Weeks) | non-specified | 1 | 0 | 0 | 0 | 0 |
| Randomized in Phase B (26 Weeks) | poor/non-compliance | 3 | 1 | 3 | 0 | 0 |
| Randomized in Phase B (26 Weeks) | Withdrawal by Subject | 35 | 14 | 19 | 15 | 19 |
Baseline characteristics
| Characteristic | Placebo | Apixaban 2.5mg BID | Apixaban 10mg QD | Apixaban 10mg BID | Apixaban 20 mg QD | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 60.5 years STANDARD_DEVIATION 11.25 | 61.1 years STANDARD_DEVIATION 11.64 | 60.7 years STANDARD_DEVIATION 11.35 | 60.3 years STANDARD_DEVIATION 11 | 60.9 years STANDARD_DEVIATION 11.95 | 60.7 years STANDARD_DEVIATION 11.38 |
| Age, Customized Greater than (>) 75 years | 67 participants | 45 participants | 39 participants | 30 participants | 32 participants | 213 participants |
| Age, Customized Greater than, equal to 65 and < 75 years | 170 participants | 85 participants | 82 participants | 53 participants | 57 participants | 447 participants |
| Age, Customized Less than (<) 65 years | 374 participants | 187 participants | 197 participants | 165 participants | 132 participants | 1055 participants |
| Region of Enrollment Austria | 4 participants | 2 participants | 2 participants | 4 participants | 2 participants | 14 participants |
| Region of Enrollment Belgium | 20 participants | 11 participants | 9 participants | 10 participants | 12 participants | 62 participants |
| Region of Enrollment Canada | 81 participants | 47 participants | 44 participants | 26 participants | 21 participants | 219 participants |
| Region of Enrollment Denmark | 16 participants | 14 participants | 15 participants | 5 participants | 4 participants | 54 participants |
| Region of Enrollment France | 21 participants | 9 participants | 8 participants | 8 participants | 10 participants | 56 participants |
| Region of Enrollment Germany | 34 participants | 12 participants | 14 participants | 17 participants | 18 participants | 95 participants |
| Region of Enrollment Israel | 55 participants | 29 participants | 32 participants | 26 participants | 21 participants | 163 participants |
| Region of Enrollment Italy | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants | 2 participants |
| Region of Enrollment Poland | 61 participants | 21 participants | 19 participants | 34 participants | 31 participants | 166 participants |
| Region of Enrollment Russian Federation | 156 participants | 93 participants | 82 participants | 59 participants | 52 participants | 442 participants |
| Region of Enrollment Spain | 36 participants | 11 participants | 16 participants | 17 participants | 19 participants | 99 participants |
| Region of Enrollment Sweden | 42 participants | 21 participants | 24 participants | 12 participants | 12 participants | 111 participants |
| Region of Enrollment United Kingdom | 15 participants | 7 participants | 9 participants | 5 participants | 5 participants | 41 participants |
| Region of Enrollment United States | 69 participants | 40 participants | 44 participants | 24 participants | 14 participants | 191 participants |
| Sex: Female, Male Female | 157 Participants | 75 Participants | 86 Participants | 45 Participants | 50 Participants | 413 Participants |
| Sex: Female, Male Male | 454 Participants | 242 Participants | 232 Participants | 203 Participants | 171 Participants | 1302 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 122 / 315 | 101 / 315 | 175 / 599 | 84 / 244 | 30 / 108 | 67 / 218 | 22 / 119 | 80 / 362 |
| serious Total, serious adverse events | 72 / 315 | 73 / 315 | 125 / 599 | 55 / 244 | 22 / 108 | 36 / 218 | 19 / 119 | 56 / 362 |
Outcome results
Primary
Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Treatment Period- Treated Participants With Placebo or Apixaban Low Doses
Bleeding was assessed using the International Society on Thrombosis and Hemostasis (ISTH) guidelines. Events were adjudicated by the Clinical Events Committee (CEC). Event rate was number of participants with events divided by the number of participants treated, measured as a percentage (%). The primary outcome is based on data for the placebo and 2 apixaban low-dose groups (2.5 mg BID and 10 mg QD) combined across Phase A and Phase B. The analyses of Phase B data across all doses of apixaban are secondary because of the premature termination of the apixaban high-dose groups (10mg BID, 20mg QD) and the resulting lower duration of exposure for these groups.
Time frame: From first dose of study drug (Day 1) to last dose plus 2 days, up to Year 2 of the Study
Population: Participants who received at least one dose of placebo or low dose apixaban. Due to the premature termination of the 2 apixaban high-dose groups (10 mg BID and 20 mg QD) in Phase B, the primary analyses reported are based on data for the placebo and 2 apixaban low-dose groups (2.5 mg BID and 10 mg QD) combined across Phase A and Phase B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Treatment Period- Treated Participants With Placebo or Apixaban Low Doses | 3.0 percentage of participants |
| Apixaban 2.5mg BID | Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Treatment Period- Treated Participants With Placebo or Apixaban Low Doses | 5.7 percentage of participants |
| Apixaban 10mg QD | Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Treatment Period- Treated Participants With Placebo or Apixaban Low Doses | 7.9 percentage of participants |
95% CI: [-1, 5.4]
95% CI: [0.4, 7.3]
Secondary
Event Rate for Adjudicated All Bleeding Events During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B
Bleeding was assessed using the ISTH guidelines. Events were adjudicated by the CEC. Event rate was number of participants with events divided by the number of participants treated (%). All bleeding events included major bleeding, clinically relevant non-major bleeding and minor bleeding. Phase B Adjusted Treatment Period=safety events occurring in the period from first dose through 2 days (or through 30 days for SAE tabulations) after the earliest of last dose date or 1-Oct-2007 (termination date for the 10 mg BID group).
Time frame: From first dose (Day 1) to last dose, plus 2 days (plus 30 days for SAEs), up to high dose termination, 1 October 2007
Population: Participants concomitantly randomized in Phase B who received at least one dose of placebo or apixaban were summarized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate for Adjudicated All Bleeding Events During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B | 6.1 percentage of participants |
| Apixaban 2.5mg BID | Event Rate for Adjudicated All Bleeding Events During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B | 15.1 percentage of participants |
| Apixaban 10mg QD | Event Rate for Adjudicated All Bleeding Events During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B | 17.6 percentage of participants |
| Apixaban 10mg BID | Event Rate for Adjudicated All Bleeding Events During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B | 24.2 percentage of participants |
| Apixaban 20 mg QD | Event Rate for Adjudicated All Bleeding Events During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B | 23.9 percentage of participants |
95% CI: [1.8, 14.9]
95% CI: [3.4, 18.4]
95% CI: [11.6, 23.2]
95% CI: [5.6, 15.1]
Secondary
Event Rate for Adjudicated All Bleeding Events During the Treatment Period - Treated Participants With Placebo or Apixaban Low Doses
Bleeding was assessed using the International Society on Thrombosis and Hemostasis (ISTH) guidelines. Events were adjudicated by the Clinical Events Committee (CEC). Event rate was number of participants with events divided by the number of participants treated (%). All bleeding events includes major bleeding, clinically relevant non-major bleeding and minor bleeding. Treatment Period refers to the period from first dose through 2 days, or through 30 days for Serious Adverse Event (SAE) tabulations, after discontinuation of study drug. Data in this outcome are combined across Phase A and Phase B.
Time frame: first dose (Day 1) to last dose plus 2 days (or for SAEs, plus 30 days), up to Year 2 of the Study
Population: Participants who received at least one dose of placebo or low dose apixaban are summarized. The analyses reported are based on data for the placebo and 2 apixaban low-dose groups (2.5 mg BID and 10 mg QD) combined across Phase A and Phase B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate for Adjudicated All Bleeding Events During the Treatment Period - Treated Participants With Placebo or Apixaban Low Doses | 10.5 percentage of participants |
| Apixaban 2.5mg BID | Event Rate for Adjudicated All Bleeding Events During the Treatment Period - Treated Participants With Placebo or Apixaban Low Doses | 20.6 percentage of participants |
| Apixaban 10mg QD | Event Rate for Adjudicated All Bleeding Events During the Treatment Period - Treated Participants With Placebo or Apixaban Low Doses | 22.5 percentage of participants |
95% CI: [1.8, 11.3]
95% CI: [4.8, 15.2]
Secondary
Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Phase B Adjusted Treatment Period- Treated Participants Randomized in Phase B
Bleeding was assessed using ISTH guidelines. Events were adjudicated by the CEC. Event rate was number of participants with events divided by the number of participants treated, measured as a percentage (%). The analyses of Phase B data across all doses of apixaban are secondary because of the premature termination of the apixaban high-dose groups and the lower duration of exposure. Phase B Adjusted Treatment Period=safety events occurring in the period from first dose through 2 days (or through 30 days for SAE tabulations) after the earliest of last dose date or 1-Oct-2007 (termination date for the 10 mg BID group).
Time frame: From first dose (Day 1) to last dose, plus 2 days (plus 30 days for SAEs), up to high dose termination, 1 October 2007
Population: Participants randomized in Phase B only who received at least one dose of placebo or apixaban were summarized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Phase B Adjusted Treatment Period- Treated Participants Randomized in Phase B | 0.8 percentage of participants |
| Apixaban 2.5mg BID | Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Phase B Adjusted Treatment Period- Treated Participants Randomized in Phase B | 5.0 percentage of participants |
| Apixaban 10mg QD | Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Phase B Adjusted Treatment Period- Treated Participants Randomized in Phase B | 5.6 percentage of participants |
| Apixaban 10mg BID | Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Phase B Adjusted Treatment Period- Treated Participants Randomized in Phase B | 7.8 percentage of participants |
| Apixaban 20 mg QD | Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Phase B Adjusted Treatment Period- Treated Participants Randomized in Phase B | 7.3 percentage of participants |
95% CI: [0, 8.1]
95% CI: [0, 9.3]
95% CI: [3.4, 10.5]
95% CI: [1.4, 8]
Secondary
Event Rate of Confirmed Adjudicated Major Bleeding During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B
Bleeding was assessed using the ISTH guidelines. Events were adjudicated by the CEC. Event rate was number of participants with events divided by the number of participants treated (%).
Time frame: From first dose (Day 1) to last dose, plus 2 days (plus 30 days for SAEs), up to high dose termination, 1 October 2007
Population: Participants concomitantly randomized in Phase B who received at least one dose of placebo or apixaban were summarized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate of Confirmed Adjudicated Major Bleeding During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B | 0.0 percentage of participants |
| Apixaban 2.5mg BID | Event Rate of Confirmed Adjudicated Major Bleeding During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B | 0.8 percentage of participants |
| Apixaban 10mg QD | Event Rate of Confirmed Adjudicated Major Bleeding During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B | 0.0 percentage of participants |
| Apixaban 10mg BID | Event Rate of Confirmed Adjudicated Major Bleeding During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B | 2.9 percentage of participants |
| Apixaban 20 mg QD | Event Rate of Confirmed Adjudicated Major Bleeding During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B | 4.1 percentage of participants |
95% CI: [-0.9, 2.6]
95% CI: [0.6, 5.1]
95% CI: [1.3, 6.9]
Secondary
Event Rate of Confirmed Adjudicated Major Bleeding During the Treatment Period- Treated Participants With Placebo or Apixaban Low Doses
Bleeding was assessed using the ISTH guidelines. Events were adjudicated by the Clinical Events Committee. Event rate was number of participants with events divided by the number of participants treated, measured as a percentage (%).
Time frame: from first dose (Day 1) to last dose plus 2 days, up to Year 2 of the Study
Population: Participants who received at least one dose of placebo or low dose apixaban were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate of Confirmed Adjudicated Major Bleeding During the Treatment Period- Treated Participants With Placebo or Apixaban Low Doses | 0.8 percentage of participants |
| Apixaban 2.5mg BID | Event Rate of Confirmed Adjudicated Major Bleeding During the Treatment Period- Treated Participants With Placebo or Apixaban Low Doses | 1.6 percentage of participants |
| Apixaban 10mg QD | Event Rate of Confirmed Adjudicated Major Bleeding During the Treatment Period- Treated Participants With Placebo or Apixaban Low Doses | 1.9 percentage of participants |
95% CI: [-1.3, 2]
95% CI: [-1.1, 2.7]
Secondary
Number of Participants With a Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, and Non-Hemorrhagic Stroke During the Intended Treatment Period - Randomized Participants
Events were adjudicated by the Clinical Events Committee (CEC). Event rate was number of participants with events divided by the number of participants treated (%). Intended Treatment Period refers to the period starting on the day of randomization and ending 182 days after the day of randomization (for a total period duration of 183 days). Data in this outcome are combined across Phase A and Phase B
Time frame: Day of randomization to 182 days after day of randomization (183 days)
Population: Randomized participants were summarized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With a Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, and Non-Hemorrhagic Stroke During the Intended Treatment Period - Randomized Participants | 54 participants |
| Apixaban 2.5mg BID | Number of Participants With a Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, and Non-Hemorrhagic Stroke During the Intended Treatment Period - Randomized Participants | 24 participants |
| Apixaban 10mg QD | Number of Participants With a Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, and Non-Hemorrhagic Stroke During the Intended Treatment Period - Randomized Participants | 20 participants |
95% CI: [0.44, 1.17]
95% CI: [0.37, 1.07]
Secondary
Number of Participants With a Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia and Non-Hemorrhagic Stroke During the Intended Treatment Period - Randomized Participants
Events were adjudicated by the Clinical Events Committee (CEC). Intended Treatment Period refers to the period starting on the day of randomization and ending 182 days after the day of randomization (for a total period duration of 183 days). Data in this outcome are combined across Phase A and Phase B.
Time frame: Randomization to 182 days after randomization (183 days)
Population: Participants who randomized to placebo or low dose apixaban are summarized. Due to the premature termination of the 2 apixaban high-dose groups (10 mg BID and 20 mg QD) in Phase B, the analyses reported are based on data for the placebo and 2 apixaban low-dose groups (2.5 mg BID and 10 mg QD) combined across Phase A and Phase B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With a Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia and Non-Hemorrhagic Stroke During the Intended Treatment Period - Randomized Participants | 53 participants |
| Apixaban 2.5mg BID | Number of Participants With a Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia and Non-Hemorrhagic Stroke During the Intended Treatment Period - Randomized Participants | 24 participants |
| Apixaban 10mg QD | Number of Participants With a Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia and Non-Hemorrhagic Stroke During the Intended Treatment Period - Randomized Participants | 19 participants |
95% CI: [0.44, 1.19]
95% CI: [0.35, 1.04]
Secondary
Number of Participants With Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B
Phase B Adjusted Intended Treatment Period=day of randomization and ends on termination date of high dose apixaban, 1-Oct-2007. The analyses of Phase B data across all doses of apixaban are secondary due to the premature termination of the apixaban high dose groups and the lower duration of exposure.
Time frame: Day of randomization and ends on high dose termination date, 1-Oct-2007
Population: Participants who were concomitantly randomized in Phase B only were summarized (start of Phase B, March 2007, to termination of high doses in Phase B, October 2007) .
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B | 16 participants |
| Apixaban 2.5mg BID | Number of Participants With Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B | 6 participants |
| Apixaban 10mg QD | Number of Participants With Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B | 4 participants |
| Apixaban 10mg BID | Number of Participants With Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B | 8 participants |
| Apixaban 20 mg QD | Number of Participants With Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B | 7 participants |
95% CI: [0.44, 2.88]
95% CI: [0.29, 2.57]
95% CI: [0.3, 1.66]
95% CI: [0.3, 1.74]
Secondary
Number of Participants With Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B
Phase B Adjusted Intended Treatment Period=day of randomization and ends on 1-Oct-2007. The analyses of Phase B data across all doses of apixaban are secondary due to the premature termination of the apixaban high dose groups and the lower duration of exposure.
Time frame: Day of randomization up to high dose termination, 1-Oct-2007
Population: Participants who were concomitantly randomized in Phase B were summarized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B | 16 participants |
| Apixaban 2.5mg BID | Number of Participants With Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B | 6 participants |
| Apixaban 10mg QD | Number of Participants With Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B | 4 participants |
| Apixaban 10mg BID | Number of Participants With Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B | 8 participants |
| Apixaban 20 mg QD | Number of Participants With Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B | 7 participants |
95% CI: [0.44, 2.88]
95% CI: [0.29, 2.57]
95% CI: [0.3, 1.66]
95% CI: [0.3, 1.74]