Atrial Fibrillation, Percutaneous Coronary Intervention
Conditions
Keywords
Atrial Fibrillation, Irregular heart beat, rivaroxaban, aspirin, clopidogrel, prasugrel, ticagrelor, vitamin K antagonist
Brief summary
The primary purpose of this study is to evaluate the safety for 2 different rivaroxaban treatment strategies and one Vitamin K Antagonist (VKA) treatment strategy utilizing various combinations of dual antiplatelet therapy (DAPT) or low-dose aspirin (ASA) or clopidogrel (or prasugrel or ticagrelor).
Detailed description
This is an open-label (both physician and participant know the treatment that the participant receives), randomized (study medication is assigned by chance), multicenter clinical study assessing the safety of 2 rivaroxaban treatment strategies and one vitamin K antagonist (VKA) treatment strategy in participants, who have paroxysmal, persistent, or permanent non-valvular atrial fibrillation (AF) and have had a percutaneous coronary intervention (PCI) with stent placement. A target of 2,100 participants will be randomized into the study, with approximately 700 participants in each treatment strategy group. The randomization will be stratified by the intended duration of DAPT (1, 6, or 12 months). The study consists of a screening phase, a 12-month open-label treatment phase, and an end-of-treatment/early withdrawal visit. The total duration of participation in the study for each participant is approximately 12 months.
Interventions
One 2.5 mg tablet twice daily for up to twelve months
One 15 mg tablet once daily for up to twelve months
One 10 mg tablet once daily for up to twelve months
DRUGaspirin (ASA)
Low-dose aspirin tablet once daily for twelve months
Dose-adjusted VKA tablet (target International Normalized Ratio (INR) 2.0 to 3.0) once daily for twelve months
DRUGclopidogrel
One 75 mg tablet once daily for up to twelve months
DRUGprasugrel
One 10 mg tablet once daily for up to twelve months
DRUGticagrelor
One 90 mg tablet twice daily for up to twelve months
Sponsors
Bayer
Janssen Scientific Affairs, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a documented medical history of paroxysmal, persistent, or permanent non-valvular atrial fibrillation (AF) * Have undergone percutaneous coronary intervention (PCI) procedure (with stent placement) for primary atherosclerotic disease * Must have an international normalized ratio (INR) of 2.5 or below to be randomized * Women must be postmenopausal before entry or practicing a highly effective method of birth control when heterosexually active * Be willing and able to adhere to the prohibitions and restrictions specified in the study protocol
Exclusion criteria
* Have any condition that contraindicates anticoagulant or antiplatelet therapy or would have an unacceptable risk of bleeding, such as, but not limited to: platelet count \<90,000/microliter at screening, history of intracranial hemorrhage, 12 month history of clinically significant gastrointestinal bleeding, non-VKA induced elevated prothrombin time (PT) at screening * Have anemia of unknown cause with a hemoglobin level \<10 g/dL (\<6.21 mmol/L) * Have a history of stroke or Transient Ischemic Attack (TIA) * Have a calculated Creatinine Clearance (CrCl) \<30 mL/min at screening * Have known significant liver disease or liver function test (LFT) abnormalities * Have any severe condition that would limit life expectancy to less than 12 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinically Significant Bleeding | Up to Month 12 | Clinically significant bleeding is a composite of Thrombolysis in Myocardial Infarction (TIMI) major bleeding, minor bleeding, and bleeding requiring medical attention (BRMA). TIMI major bleeding is defined as any symptomatic intracranial hemorrhage, clinically overt signs of hemorrhage (including imaging) associated with a drop in hemoglobin of greater than or equal to (\>=) 5 grams per deciliter (g/dL) (or when the hemoglobin concentration is not available, an absolute drop in hematocrit of \>=15 percent (%)). TIMI minor bleeding event is defined as any clinically overt sign of hemorrhage (including imaging) that is associated with a fall in hemoglobin concentration of 3 to less than (\<) 5 g/dL (or, when hemoglobin concentration is not available, a fall in hematocrit of 9 percent to \<15 percent). A BRMA event is defined as any bleeding event that requires medical treatment, surgical treatment, or laboratory evaluation, and does not meet criteria for a major or minor bleeding event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Minor Bleeding | Up to Month 12 and end of DAPT-Month 1, 6 and 12 | TIMI minor bleeding event is defined as any clinically overt sign of hemorrhage (including imaging) that is associated with a fall in hemoglobin concentration of 3 to \<5 g/dL (or, when hemoglobin concentration is not available, a fall in hematocrit of 9 percent to \<15 percent). |
| Percentage of Participants With Bleeding Requiring Medical Attention (BRMA) | Up to Month 12 and end of DAPT-Month 1, 6 and 12 | A BRMA event is defined as any bleeding event that requires medical treatment, surgical treatment, or laboratory evaluation, and does not meet criteria for a major or minor bleeding event. |
| Percentage of Participants With Composite of Adverse Cardiovascular Events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke) | Up to Month 12 and end of DAPT-Month 1, 6 and 12 | Percentage of participants who experienced adverse cardiovascular events (cardiovascular death, myocardial Infarction (MI) and stroke) collectively, were assessed. |
| Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | Up to Month 12 and end of DAPT-Month 1, 6 and 12 | TIMI major bleeding is defined as any symptomatic intracranial hemorrhage, Clinically overt signs of hemorrhage (including imaging) associated with a drop in hemoglobin of \>= 5 g/dL (or when the hemoglobin concentration is not available, an absolute drop in hematocrit of \>=15 percent). |
| Percentage of Participants With Myocardial Infarction | Up to Month 12 and end of DAPT-Month 1, 6 and 12 | The percentage of participants with the first occurrence of Myocardial Infarction were evaluated. |
| Percentage of Participants With Stroke | Up to Month 12 and end of DAPT-Month 1, 6 and 12 | The percentage of participants with the first occurrence of Stroke were evaluated. |
| Percentage of Participants With Stent Thrombosis | Up to Month 12 and end of DAPT-Month 1, 6 and 12 | The percentage of participants with the first occurrence of stent thrombosis were evaluated. |
| Percentage of Participants With Cardiovascular Death | Up to Month 12 and end of DAPT-Month 1, 6 and 12 | The percentage of participants with the first occurrence of cardiovascular death were evaluated. |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, Czechia, Denmark, France, Germany, Malaysia, Mexico, Netherlands, Poland, Romania, Russia, South Africa, South Korea, Sweden, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rivaroxaban 15 mg Participants received rivaroxaban 15 milligram (mg) or 10 mg (for participants with moderate renal impairment \[creatinine clearance (CrCl): 30 to less than (\<) 50 milliliter per minute (mL/min)\]) once daily plus background therapy with clopidogrel 75 mg once daily or alternate P2Y12 inhibitor (prasugrel 10 mg per day or ticagrelor 90 mg twice daily) for 12 months. | 709 |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) Participants received rivaroxaban 2.5 mg twice daily plus background dual antiplatelet therapy (DAPT) with low-dose acetylsalicylic acid (ASA) 75 to 100 mg per day and clopidogrel 75 mg once daily (or alternate P2Y12 inhibitor \[prasugrel or ticagrelor\]) for an intended DAPT duration of 1, 6, or 12 months. Only participants with an intended DAPT duration of 1 or 6-month transitioned to receive rivaroxaban 15 mg or 10 mg (for participants with moderate renal impairment) once daily plus background single antiplatelet therapy with low-dose ASA for the rest of the period up to Month 12. | 709 |
| Vitamin K Antagonist (VKA) Participants received dose adjusted (to a target of international normalized ratio \[INR\] 2.0 to 3.0 \[or target INR 2.0 to 2.5\]) vitamin K antagonist (VKA) \[example warfarin, acenocoumarol; assigned by the investigator according to approved formulations) once daily plus background DAPT (clopidogrel 75 mg \[or alternate P2Y12 inhibitor (prasugrel or ticagrelor)\] plus low-dose ASA \[75 to 100 mg\] daily) for an intended DAPT duration of 1, 6, or 12 months. Only participants with an intended DAPT duration of 1 or 6-month transitioned to receive dose-adjusted VKA plus background single antiplatelet therapy with low-dose ASA for the rest of the period up to Month 12. | 706 |
| Total | 2,124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 91 | 77 | 76 |
| Overall Study | Death | 20 | 22 | 22 |
| Overall Study | Other | 12 | 17 | 37 |
| Overall Study | Physician Decision | 11 | 5 | 12 |
| Overall Study | Protocol Violation | 3 | 7 | 7 |
| Overall Study | Subject Decision | 19 | 21 | 57 |
| Overall Study | Withdrawal by consent | 3 | 3 | 3 |
Baseline characteristics
| Characteristic | Rivaroxaban 15 mg | Total | Vitamin K Antagonist (VKA) | Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) |
|---|---|---|---|---|
| Age, Continuous | 70.4 years STANDARD_DEVIATION 9.12 | 70.1 years STANDARD_DEVIATION 8.97 | 69.9 years STANDARD_DEVIATION 8.67 | 70 years STANDARD_DEVIATION 9.11 |
| Region of Enrollment Argentina | 32 participants | 82 participants | 23 participants | 27 participants |
| Region of Enrollment Australia | 3 participants | 15 participants | 5 participants | 7 participants |
| Region of Enrollment Belgium | 14 participants | 52 participants | 20 participants | 18 participants |
| Region of Enrollment Brazil | 14 participants | 41 participants | 13 participants | 14 participants |
| Region of Enrollment Bulgaria | 67 participants | 221 participants | 74 participants | 80 participants |
| Region of Enrollment Canada | 23 participants | 66 participants | 19 participants | 24 participants |
| Region of Enrollment Chile | 5 participants | 18 participants | 6 participants | 7 participants |
| Region of Enrollment Czech Republic | 17 participants | 40 participants | 14 participants | 9 participants |
| Region of Enrollment Denmark | 2 participants | 12 participants | 8 participants | 2 participants |
| Region of Enrollment France | 33 participants | 84 participants | 25 participants | 26 participants |
| Region of Enrollment Germany | 96 participants | 295 participants | 101 participants | 98 participants |
| Region of Enrollment Italy | 26 participants | 72 participants | 20 participants | 26 participants |
| Region of Enrollment Korea, Republic of | 11 participants | 39 participants | 17 participants | 11 participants |
| Region of Enrollment Malaysia | 1 participants | 11 participants | 5 participants | 5 participants |
| Region of Enrollment Mexico | 7 participants | 13 participants | 3 participants | 3 participants |
| Region of Enrollment Netherlands | 24 participants | 68 participants | 27 participants | 17 participants |
| Region of Enrollment Poland | 71 participants | 218 participants | 69 participants | 78 participants |
| Region of Enrollment Romania | 15 participants | 50 participants | 19 participants | 16 participants |
| Region of Enrollment Russian Federation | 90 participants | 265 participants | 89 participants | 86 participants |
| Region of Enrollment South Africa | 1 participants | 5 participants | 2 participants | 2 participants |
| Region of Enrollment Sweden | 15 participants | 47 participants | 18 participants | 14 participants |
| Region of Enrollment Taiwan, Province of China | 8 participants | 25 participants | 9 participants | 8 participants |
| Region of Enrollment Turkey | 11 participants | 43 participants | 18 participants | 14 participants |
| Region of Enrollment Ukraine | 19 participants | 60 participants | 17 participants | 24 participants |
| Region of Enrollment United Kingdom | 48 participants | 131 participants | 39 participants | 44 participants |
| Region of Enrollment United States | 56 participants | 151 participants | 46 participants | 49 participants |
| Sex: Female, Male Female | 181 Participants | 543 Participants | 188 Participants | 174 Participants |
| Sex: Female, Male Male | 528 Participants | 1581 Participants | 518 Participants | 535 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 174 / 696 | 210 / 706 | 234 / 697 |
| serious Total, serious adverse events | 237 / 696 | 225 / 706 | 271 / 697 |
Outcome results
Primary
Percentage of Participants With Clinically Significant Bleeding
Clinically significant bleeding is a composite of Thrombolysis in Myocardial Infarction (TIMI) major bleeding, minor bleeding, and bleeding requiring medical attention (BRMA). TIMI major bleeding is defined as any symptomatic intracranial hemorrhage, clinically overt signs of hemorrhage (including imaging) associated with a drop in hemoglobin of greater than or equal to (\>=) 5 grams per deciliter (g/dL) (or when the hemoglobin concentration is not available, an absolute drop in hematocrit of \>=15 percent (%)). TIMI minor bleeding event is defined as any clinically overt sign of hemorrhage (including imaging) that is associated with a fall in hemoglobin concentration of 3 to less than (\<) 5 g/dL (or, when hemoglobin concentration is not available, a fall in hematocrit of 9 percent to \<15 percent). A BRMA event is defined as any bleeding event that requires medical treatment, surgical treatment, or laboratory evaluation, and does not meet criteria for a major or minor bleeding event.
Time frame: Up to Month 12
Population: The safety analysis set is defined as all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rivaroxaban 15 mg | Percentage of Participants With Clinically Significant Bleeding | 15.7 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Clinically Significant Bleeding | 16.6 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Clinically Significant Bleeding | 24.0 percentage of participants |
p-value: <0.00195% CI: [0.47, 0.76]Log Rank
p-value: <0.00195% CI: [0.5, 0.8]Log Rank
Secondary
Percentage of Participants With Bleeding Requiring Medical Attention (BRMA)
A BRMA event is defined as any bleeding event that requires medical treatment, surgical treatment, or laboratory evaluation, and does not meet criteria for a major or minor bleeding event.
Time frame: Up to Month 12 and end of DAPT-Month 1, 6 and 12
Population: The safety analysis set is defined as all randomized participants who received at least 1 dose of study drug. Here 'n' signifies number of participants analyzed at specific time-point in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rivaroxaban 15 mg | Percentage of Participants With Bleeding Requiring Medical Attention (BRMA) | Up to Month 12 (n= 696, 706, 697) | 13.4 percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Bleeding Requiring Medical Attention (BRMA) | End of DAPT-1 Month (n= 0, 108, 113) | NA percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Bleeding Requiring Medical Attention (BRMA) | End of DAPT-6 Month (n= 0, 248, 243) | NA percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Bleeding Requiring Medical Attention (BRMA) | End of DAPT-12 Month (n= 0, 350, 341) | NA percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Bleeding Requiring Medical Attention (BRMA) | End of DAPT-12 Month (n= 0, 350, 341) | 14.9 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Bleeding Requiring Medical Attention (BRMA) | Up to Month 12 (n= 696, 706, 697) | 14.4 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Bleeding Requiring Medical Attention (BRMA) | End of DAPT-6 Month (n= 0, 248, 243) | 12.9 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Bleeding Requiring Medical Attention (BRMA) | End of DAPT-1 Month (n= 0, 108, 113) | 16.7 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Bleeding Requiring Medical Attention (BRMA) | End of DAPT-12 Month (n= 0, 350, 341) | 18.2 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Bleeding Requiring Medical Attention (BRMA) | End of DAPT-1 Month (n= 0, 108, 113) | 18.6 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Bleeding Requiring Medical Attention (BRMA) | End of DAPT-6 Month (n= 0, 248, 243) | 23 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Bleeding Requiring Medical Attention (BRMA) | Up to Month 12 (n= 696, 706, 697) | 19.9 percentage of participants |
p-value: <0.00195% CI: [0.47, 0.8]Log Rank
p-value: 0.00295% CI: [0.52, 0.86]Log Rank
Secondary
Percentage of Participants With Cardiovascular Death
The percentage of participants with the first occurrence of cardiovascular death were evaluated.
Time frame: Up to Month 12 and end of DAPT-Month 1, 6 and 12
Population: The safety analysis set is defined as all randomized participants who received at least 1 dose of study drug. Here 'N' signifies number of participants who were evaluable for this outcome measure, 'n' signifies number of participants analyzed at specific time-point in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rivaroxaban 15 mg | Percentage of Participants With Cardiovascular Death | Up to Month 12 (n= 694, 704, 695) | 2.2 percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Cardiovascular Death | End of DAPT-1 Month (n= 0, 108, 112) | NA percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Cardiovascular Death | End of DAPT-6 Month (n= 0, 248, 243) | NA percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Cardiovascular Death | End of DAPT-12 Month (n= 0, 348, 340) | NA percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Cardiovascular Death | End of DAPT-12 Month (n= 0, 348, 340) | 1.7 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Cardiovascular Death | Up to Month 12 (n= 694, 704, 695) | 2 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Cardiovascular Death | End of DAPT-6 Month (n= 0, 248, 243) | 2.4 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Cardiovascular Death | End of DAPT-1 Month (n= 0, 108, 112) | 1.9 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Cardiovascular Death | End of DAPT-12 Month (n= 0, 348, 340) | 1.5 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Cardiovascular Death | End of DAPT-1 Month (n= 0, 108, 112) | 1.8 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Cardiovascular Death | End of DAPT-6 Month (n= 0, 248, 243) | 1.6 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Cardiovascular Death | Up to Month 12 (n= 694, 704, 695) | 1.6 percentage of participants |
p-value: 0.52395% CI: [0.59, 2.8]Log Rank
p-value: 0.66495% CI: [0.54, 2.62]Log Rank
Secondary
Percentage of Participants With Composite of Adverse Cardiovascular Events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke)
Percentage of participants who experienced adverse cardiovascular events (cardiovascular death, myocardial Infarction (MI) and stroke) collectively, were assessed.
Time frame: Up to Month 12 and end of DAPT-Month 1, 6 and 12
Population: The safety analysis set is defined as all randomized participants who received at least 1 dose of study drug. Here 'N' signifies number of participants who were evaluable for this outcome measure, 'n' signifies number of participants analyzed at specific time-point in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rivaroxaban 15 mg | Percentage of Participants With Composite of Adverse Cardiovascular Events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke) | Up to Month 12 (n= 694, 704, 695) | 5.9 percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Composite of Adverse Cardiovascular Events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke) | End of DAPT-1 Month (n= 0, 108, 112) | NA percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Composite of Adverse Cardiovascular Events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke) | End of DAPT-6 Month (n= 0, 248, 243) | NA percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Composite of Adverse Cardiovascular Events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke) | End of DAPT-12 Month (n= 0, 348, 340) | NA percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Composite of Adverse Cardiovascular Events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke) | End of DAPT-12 Month (n= 0, 348, 340) | 4 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Composite of Adverse Cardiovascular Events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke) | Up to Month 12 (n= 694, 704, 695) | 5.1 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Composite of Adverse Cardiovascular Events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke) | End of DAPT-6 Month (n= 0, 248, 243) | 6.5 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Composite of Adverse Cardiovascular Events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke) | End of DAPT-1 Month (n= 0, 108, 112) | 5.6 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Composite of Adverse Cardiovascular Events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke) | End of DAPT-12 Month (n= 0, 348, 340) | 6.5 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Composite of Adverse Cardiovascular Events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke) | End of DAPT-1 Month (n= 0, 108, 112) | 4.5 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Composite of Adverse Cardiovascular Events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke) | End of DAPT-6 Month (n= 0, 248, 243) | 3.7 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Composite of Adverse Cardiovascular Events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke) | Up to Month 12 (n= 694, 704, 695) | 5.2 percentage of participants |
p-value: 0.7595% CI: [0.69, 1.68]Log Rank
p-value: 0.76595% CI: [0.59, 1.48]Log Rank
Secondary
Percentage of Participants With Myocardial Infarction
The percentage of participants with the first occurrence of Myocardial Infarction were evaluated.
Time frame: Up to Month 12 and end of DAPT-Month 1, 6 and 12
Population: The safety analysis set is defined as all randomized participants who received at least 1 dose of study drug. Here 'N' signifies number of participants who were evaluable for this outcome measure, 'n' signifies number of participants analyzed at specific time-point in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rivaroxaban 15 mg | Percentage of Participants With Myocardial Infarction | Up to Month 12 (n= 694, 704, 695) | 2.7 percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Myocardial Infarction | End of DAPT-1 Month (n= 0, 108, 112) | NA percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Myocardial Infarction | End of DAPT-6 Month (n= 0, 248, 243) | NA percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Myocardial Infarction | End of DAPT-12 Month (n= 0, 348, 340) | NA percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Myocardial Infarction | End of DAPT-12 Month (n= 0, 348, 340) | 2 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Myocardial Infarction | Up to Month 12 (n= 694, 704, 695) | 2.4 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Myocardial Infarction | End of DAPT-6 Month (n= 0, 248, 243) | 2.8 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Myocardial Infarction | End of DAPT-1 Month (n= 0, 108, 112) | 2.8 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Myocardial Infarction | End of DAPT-12 Month (n= 0, 348, 340) | 4.1 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Myocardial Infarction | End of DAPT-1 Month (n= 0, 108, 112) | 0.9 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Myocardial Infarction | End of DAPT-6 Month (n= 0, 248, 243) | 2.5 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Myocardial Infarction | Up to Month 12 (n= 694, 704, 695) | 3 percentage of participants |
p-value: 0.62595% CI: [0.46, 1.59]Log Rank
p-value: 0.37495% CI: [0.4, 1.42]Log Rank
Secondary
Percentage of Participants With Stent Thrombosis
The percentage of participants with the first occurrence of stent thrombosis were evaluated.
Time frame: Up to Month 12 and end of DAPT-Month 1, 6 and 12
Population: The safety analysis set is defined as all randomized participants who received at least 1 dose of study drug. Here 'N' signifies number of participants who were evaluable for this outcome measure, 'n' signifies number of participants analyzed at specific time-point in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rivaroxaban 15 mg | Percentage of Participants With Stent Thrombosis | Up to Month 12 (n= 694, 704, 695) | 0.7 percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Stent Thrombosis | End of DAPT-1 Month (n= 0, 108, 112) | NA percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Stent Thrombosis | End of DAPT-6 Month (n= 0, 248, 243) | NA percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Stent Thrombosis | End of DAPT-12 Month (n= 0, 348, 340) | NA percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Stent Thrombosis | End of DAPT-12 Month (n= 0, 348, 340) | 0 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Stent Thrombosis | Up to Month 12 (n= 694, 704, 695) | 0.9 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Stent Thrombosis | End of DAPT-6 Month (n= 0, 248, 243) | 1.6 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Stent Thrombosis | End of DAPT-1 Month (n= 0, 108, 112) | 1.9 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Stent Thrombosis | End of DAPT-12 Month (n= 0, 348, 340) | 0.6 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Stent Thrombosis | End of DAPT-1 Month (n= 0, 108, 112) | 0.9 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Stent Thrombosis | End of DAPT-6 Month (n= 0, 248, 243) | 0.4 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Stent Thrombosis | Up to Month 12 (n= 694, 704, 695) | 0.6 percentage of participants |
p-value: 0.7995% CI: [0.32, 4.45]Log Rank
p-value: 0.57495% CI: [0.4, 5.09]Log Rank
Secondary
Percentage of Participants With Stroke
The percentage of participants with the first occurrence of Stroke were evaluated.
Time frame: Up to Month 12 and end of DAPT-Month 1, 6 and 12
Population: The safety analysis set is defined as all randomized participants who received at least 1 dose of study drug. Here 'N' signifies number of participants who were evaluable for this outcome measure, 'n' signifies number of participants analyzed at specific time-point in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rivaroxaban 15 mg | Percentage of Participants With Stroke | Up to Month 12 (n= 694, 704, 695) | 1.2 percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Stroke | End of DAPT-1 Month (n= 0, 108, 112) | NA percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Stroke | End of DAPT-6 Month (n= 0, 248, 243) | NA percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Stroke | End of DAPT-12 Month (n= 0, 348, 340) | NA percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Stroke | End of DAPT-12 Month (n= 0, 348, 340) | 0.6 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Stroke | Up to Month 12 (n= 694, 704, 695) | 1.4 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Stroke | End of DAPT-6 Month (n= 0, 248, 243) | 2.4 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Stroke | End of DAPT-1 Month (n= 0, 108, 112) | 1.9 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Stroke | End of DAPT-12 Month (n= 0, 348, 340) | 1.2 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Stroke | End of DAPT-1 Month (n= 0, 108, 112) | 2.7 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Stroke | End of DAPT-6 Month (n= 0, 248, 243) | 0 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Stroke | Up to Month 12 (n= 694, 704, 695) | 1 percentage of participants |
p-value: 0.89195% CI: [0.39, 2.96]Log Rank
p-value: 0.5395% CI: [0.52, 3.58]Log Rank
Secondary
Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding
TIMI major bleeding is defined as any symptomatic intracranial hemorrhage, Clinically overt signs of hemorrhage (including imaging) associated with a drop in hemoglobin of \>= 5 g/dL (or when the hemoglobin concentration is not available, an absolute drop in hematocrit of \>=15 percent).
Time frame: Up to Month 12 and end of DAPT-Month 1, 6 and 12
Population: The safety analysis set is defined as all randomized participants who received at least 1 dose of study drug. Here, 'n' signifies number of participants analyzed at specific time-point in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rivaroxaban 15 mg | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | Up to Month 12 (n= 696, 706, 697) | 2.0 percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | End of DAPT-1 Month (n= 0, 108,113) | NA percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | End of DAPT-6 Month (n= 0, 248,243) | NA percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | End of DAPT-12 Month (n= 0, 350,341) | NA percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | End of DAPT-12 Month (n= 0, 350,341) | 1.1 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | Up to Month 12 (n= 696, 706, 697) | 1.7 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | End of DAPT-6 Month (n= 0, 248,243) | 2.8 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | End of DAPT-1 Month (n= 0, 108,113) | 0.9 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | End of DAPT-12 Month (n= 0, 350,341) | 1.8 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | End of DAPT-1 Month (n= 0, 108,113) | 4.4 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | End of DAPT-6 Month (n= 0, 248,243) | 3.7 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | Up to Month 12 (n= 696, 706, 697) | 2.9 percentage of participants |
p-value: 0.23495% CI: [0.33, 1.31]Log Rank
p-value: 0.11495% CI: [0.28, 1.16]Log Rank
Secondary
Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Minor Bleeding
TIMI minor bleeding event is defined as any clinically overt sign of hemorrhage (including imaging) that is associated with a fall in hemoglobin concentration of 3 to \<5 g/dL (or, when hemoglobin concentration is not available, a fall in hematocrit of 9 percent to \<15 percent).
Time frame: Up to Month 12 and end of DAPT-Month 1, 6 and 12
Population: The safety analysis set is defined as all randomized participants who received at least 1 dose of study drug. Here 'n' signifies number of participants analyzed at specific time-point in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rivaroxaban 15 mg | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Minor Bleeding | Up to Month 12 (n= 696, 706, 697) | 1.0 percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Minor Bleeding | End of DAPT-1 Month (n= 0, 108, 113) | NA percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Minor Bleeding | End of DAPT-6 Month (n= 0, 248, 243) | NA percentage of participants |
| Rivaroxaban 15 mg | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Minor Bleeding | End of DAPT-12 Month (n= 0, 350, 341) | NA percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Minor Bleeding | End of DAPT-12 Month (n= 0, 350, 341) | 1.4 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Minor Bleeding | Up to Month 12 (n= 696, 706, 697) | 1.0 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Minor Bleeding | End of DAPT-6 Month (n= 0, 248, 243) | 0.4 percentage of participants |
| Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Minor Bleeding | End of DAPT-1 Month (n= 0, 108, 113) | 0.9 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Minor Bleeding | End of DAPT-12 Month (n= 0, 350, 341) | 1.5 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Minor Bleeding | End of DAPT-1 Month (n= 0, 108, 113) | 1.8 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Minor Bleeding | End of DAPT-6 Month (n= 0, 248, 243) | 2.5 percentage of participants |
| Vitamin K Antagonist (VKA) | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Minor Bleeding | Up to Month 12 (n= 696, 706, 697) | 1.9 percentage of participants |
p-value: 0.14495% CI: [0.2, 1.28]Log Rank
p-value: 0.13495% CI: [0.2, 1.26]Log Rank