Atrial Fibrillation, Coronary Artery Disease
Conditions
Brief summary
The study aims to evaluate the safety and effectiveness comparisons between warfarin, dabigatran, and rivaroxaban in routine clinical practice among Japanese non-valvular atrial fibrillation (NVAF) patients with concomitant coronary artery disease (CAD).
Interventions
None listed
Sponsors
Boehringer Ingelheim
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
-≥18 years of age * Has one year of look-back period prior to the index date (defined as the first date of prescription for dabigatran, rivaroxaban, or warfarin during the study period) * New users of warfarin, dabigatran, and rivaroxaban, defined as patients without historic use of any oral anticoagulants during the look-back period * Has at least 1 diagnosis of NVAF during the look-back period prior to or on the index date * Has at least 1 diagnosis of CAD during the look-back period prior to or on the index date
Exclusion criteria
* Diagnosed with end-stage renal disease, or undergo hemodialysis, or experience pregnancy during the study period * Initiate warfarin, dabigatran, rivaroxaban due to valvular Atrial Fibrillation (AF), AF associated with mechanical valve malfunction or mechanical complication of heart valve prosthesis, or rheumatic AF * Underwent joint replacement procedures or diagnosed with venous thromboembolism during the look-back period prior to or on the index date * Prescribed with more than 1 oral anticoagulation (OAC) on the index date * Prescribed with more than 2 anti-platelet drugs per prescription (triple or quadruple anti-platelet use), or prescribed with any anti-platelet injection * Patients with missing or ambiguous age or sex information
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate of Fatal or Non-fatal Major Bleeding | From the cohort entry date (first prescription of the drug of interest) to the earliest occurrence of the event (discontinuation of drug of interest, switching to another Oral Anticoagulation, loss of follow-up, death, end of the study). Up to 9 years. | Incidence rate of fatal or non-fatal major bleeding per number of person-years, defined as any blood transfusion and/or any hospitalization with associated bleeding in all three patient groups. The incidence rate was reported as the number of events (counts the first event per patient) divided by the total number of person-years at risk during follow-up (1/(1000\*person-years)). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate of Composite Outcome of Stroke/SE/MI/All-cause Mortality (Inpatient) /Major Bleeding/Major GI Bleeding/ICH | From the cohort entry date (first prescription of the drug of interest) to the earliest occurrence of the event (discontinuation of drug of interest, switching to another Oral Anticoagulation, loss of follow-up, death, end of the study). Up to 9 years. | Incidence rate of the Composite outcome of stroke/SE/MI/all-cause mortality (inpatient) /major bleeding/major GI bleeding (hospitalization due to gastrointestinal bleeding)/ICH (Intracraneal hemorrhage) per number of person-years. The incidence rate was reported as the number of events (counts the first event per patient) divided by the total number of person-years at risk during follow-up (1/(1000\*person-years)). The propensity scores were estimated using the multivariable logistic regression model. Statistical analysis for comparisons: Dabigatran-Warfarin, and Rivaroxaban-Warfarin are presented as per protocol. |
Countries
Germany
Participant flow
Recruitment details
A Real world, non-interventional cohort study based on existing data from The Medical Data Vision Co. Ltd. (Tokyo, Japan). The study aimed to make safety and effectiveness comparisons between warfarin, dabigatran, and rivaroxaban in routine clinical practice among Japanese non-valvular atrial fibrillation (NVAF) patients with concomitant Coronary Artery Disease (CAD).
Pre-assignment details
Every patient who fulfilled inclusion and exclusion criteria and agreed to participate in the study was selected until the required sample size was achieved.
Participants by arm
| Arm | Count |
|---|---|
| Warfarin All eligible Japanese on-valvular atrial fibrillation (NVAF) patients with concomitant Coronary Artery Disease (CAD), who were prescribed with warfarin. From existing data from the Japan Medical Data Vision Co. Ltd. (MDV) database, which covered all insurance types and a large population size.
The study period started on April 18th, 2011 (start of data collection) to December 31st, 2020 (end of data collection). | 12,316 |
| Dabigatran All eligible Japanese on-valvular atrial fibrillation (NVAF) patients with concomitant Coronary Artery Disease (CAD), who were prescribed with dabigatran. From existing data from the Japan Medical Data Vision Co. Ltd. (MDV) database, which covered all insurance types and a large population size.
The study period started on April 18th, 2011 (start of data collection) to December 31st, 2020 (end of data collection). | 6,712 |
| Rivaroxaban All eligible Japanese on-valvular atrial fibrillation (NVAF) patients with concomitant Coronary Artery Disease (CAD), who were prescribed with rivaroxaban. From existing data from the Japan Medical Data Vision Co. Ltd. (MDV) database, which covered all insurance types and a large population size.
The study period started on April 18th, 2011 (start of data collection) to December 31st, 2020 (end of data collection). | 20,329 |
| Total | 39,357 |
Baseline characteristics
| Characteristic | Dabigatran | Rivaroxaban | Warfarin | Total |
|---|---|---|---|---|
| Age, Continuous | 71.8 Years STANDARD_DEVIATION 10.6 | 74.2 Years STANDARD_DEVIATION 10.6 | 77.0 Years STANDARD_DEVIATION 10.2 | 74.7 Years STANDARD_DEVIATION 10.7 |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Sex: Female, Male Female | 1820 Participants | 6411 Participants | 4448 Participants | 12679 Participants |
| Sex: Female, Male Male | 4892 Participants | 13918 Participants | 7868 Participants | 26678 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Incidence Rate of Fatal or Non-fatal Major Bleeding
Incidence rate of fatal or non-fatal major bleeding per number of person-years, defined as any blood transfusion and/or any hospitalization with associated bleeding in all three patient groups. The incidence rate was reported as the number of events (counts the first event per patient) divided by the total number of person-years at risk during follow-up (1/(1000\*person-years)).
Time frame: From the cohort entry date (first prescription of the drug of interest) to the earliest occurrence of the event (discontinuation of drug of interest, switching to another Oral Anticoagulation, loss of follow-up, death, end of the study). Up to 9 years.
Population: Matched cohort of initiators of Dabigatran, Warfarin, Rivaroxaban using the inverse probability of treatment weighting (IPTW) method, identified from the Japan Medical Data Vision Co. Ltd. (MDV) database on April 18th, 2011 (start of data collection) to December 31st, 2020 (end of data collection).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran - Matched With Warfarin Using the s-IPTW Method | Incidence Rate of Fatal or Non-fatal Major Bleeding | 26 Events per 1,000 person-years |
| Warfarin - Matched With Dabigatran Using the s-IPTW Method | Incidence Rate of Fatal or Non-fatal Major Bleeding | 52 Events per 1,000 person-years |
| Rivaroxaban - Matched With Warfarin Using the s-IPTW Method | Incidence Rate of Fatal or Non-fatal Major Bleeding | 41 Events per 1,000 person-years |
| Warfarin - Matched With Rivaroxaban Using the s-IPTW Method | Incidence Rate of Fatal or Non-fatal Major Bleeding | 52 Events per 1,000 person-years |
| Dabigatran - Matched With Rivaroxaban Using the s-IPTW Method | Incidence Rate of Fatal or Non-fatal Major Bleeding | 26 Events per 1,000 person-years |
| Rivaroxaban - Matched With Dabigatran Using the s-IPTW Method | Incidence Rate of Fatal or Non-fatal Major Bleeding | 41 Events per 1,000 person-years |
p-value: <0.000195% CI: [0.402, 0.622]Regression, Cox
p-value: 0.000495% CI: [0.686, 0.896]Regression, Cox
p-value: <0.000195% CI: [0.514, 0.791]Regression, Cox
Secondary
Incidence Rate of Composite Outcome of Stroke/SE/MI/All-cause Mortality (Inpatient) /Major Bleeding/Major GI Bleeding/ICH
Incidence rate of the Composite outcome of stroke/SE/MI/all-cause mortality (inpatient) /major bleeding/major GI bleeding (hospitalization due to gastrointestinal bleeding)/ICH (Intracraneal hemorrhage) per number of person-years. The incidence rate was reported as the number of events (counts the first event per patient) divided by the total number of person-years at risk during follow-up (1/(1000\*person-years)). The propensity scores were estimated using the multivariable logistic regression model. Statistical analysis for comparisons: Dabigatran-Warfarin, and Rivaroxaban-Warfarin are presented as per protocol.
Time frame: From the cohort entry date (first prescription of the drug of interest) to the earliest occurrence of the event (discontinuation of drug of interest, switching to another Oral Anticoagulation, loss of follow-up, death, end of the study). Up to 9 years.
Population: Matched cohort of initiators of Dabigatran, Warfarin, Rivaroxaban using the inverse probability of treatment weighting (IPTW) method, identified from the Japan Medical Data Vision Co. Ltd. (MDV) database on April 18th, 2011 (start of data collection) to December 31st, 2020 (end of data collection).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran - Matched With Warfarin Using the s-IPTW Method | Incidence Rate of Composite Outcome of Stroke/SE/MI/All-cause Mortality (Inpatient) /Major Bleeding/Major GI Bleeding/ICH | 213 Events per 1,000 person-years |
| Warfarin - Matched With Dabigatran Using the s-IPTW Method | Incidence Rate of Composite Outcome of Stroke/SE/MI/All-cause Mortality (Inpatient) /Major Bleeding/Major GI Bleeding/ICH | 275 Events per 1,000 person-years |
| Rivaroxaban - Matched With Warfarin Using the s-IPTW Method | Incidence Rate of Composite Outcome of Stroke/SE/MI/All-cause Mortality (Inpatient) /Major Bleeding/Major GI Bleeding/ICH | 228 Events per 1,000 person-years |
| Warfarin - Matched With Rivaroxaban Using the s-IPTW Method | Incidence Rate of Composite Outcome of Stroke/SE/MI/All-cause Mortality (Inpatient) /Major Bleeding/Major GI Bleeding/ICH | 275 Events per 1,000 person-years |
| Dabigatran - Matched With Rivaroxaban Using the s-IPTW Method | Incidence Rate of Composite Outcome of Stroke/SE/MI/All-cause Mortality (Inpatient) /Major Bleeding/Major GI Bleeding/ICH | 213 Events per 1,000 person-years |
| Rivaroxaban - Matched With Dabigatran Using the s-IPTW Method | Incidence Rate of Composite Outcome of Stroke/SE/MI/All-cause Mortality (Inpatient) /Major Bleeding/Major GI Bleeding/ICH | 228 Events per 1,000 person-years |
p-value: <0.000195% CI: [0.714, 0.851]Regression, Cox
p-value: <0.000195% CI: [0.777, 0.88]Regression, Cox