Trial Outcomes & Findings for A Study Based on Japanese Medical Records That Looks at Bleeding Events in People With Atrial Fibrillation and Coronary Artery Disease Who Start Taking Either Dabigatran, Rivaroxaban, or Warfarin (NCT NCT05051904)

Results Overview

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)).

Recruitment status

COMPLETED

Target enrollment

39357 participants

Primary outcome timeframe

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.

Results posted on

2024-03-07

Participant Flow

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).

Every patient who fulfilled inclusion and exclusion criteria and agreed to participate in the study was selected until the required sample size was achieved.

Participant milestones

Participant milestones
Measure	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).	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).	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).
Overall Study STARTED	12316	6712	20329
Overall Study Crude	12316	6712	20329
Overall Study s-IPTW Adjusted	12231	6682	20422
Overall Study COMPLETED	12316	6712	20329
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Warfarin n=12316 Participants 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).	Dabigatran n=6712 Participants 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).	Rivaroxaban n=20329 Participants 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).	Total n=39357 Participants Total of all reporting groups
Age, Continuous	77.0 Years STANDARD_DEVIATION 10.2 • n=12316 Participants	71.8 Years STANDARD_DEVIATION 10.6 • n=6712 Participants	74.2 Years STANDARD_DEVIATION 10.6 • n=20329 Participants	74.7 Years STANDARD_DEVIATION 10.7 • n=39357 Participants
Sex: Female, Male Female	4448 Participants n=12316 Participants	1820 Participants n=6712 Participants	6411 Participants n=20329 Participants	12679 Participants n=39357 Participants
Sex: Female, Male Male	7868 Participants n=12316 Participants	4892 Participants n=6712 Participants	13918 Participants n=20329 Participants	26678 Participants n=39357 Participants
Race and Ethnicity Not Collected	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: 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).

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)).

Outcome measures

Outcome measures
Measure	Dabigatran - Matched With Warfarin Using the s-IPTW Method n=6682 Participants Matched cohort of patients with on-valvular atrial fibrillation (NVAF) with concomitant Coronary Artery Disease (CAD), who were prescribed with Dabigatran. From existing data from the Japan Medical Data Vision Co. Ltd. (MDV) database. The study period started on April 18th, 2011 (start of data collection) to December 31st, 2020 (end of data collection).	Warfarin - Matched With Dabigatran Using the s-IPTW Method n=12231 Participants Matched cohort of patients with on-valvular atrial fibrillation (NVAF) with concomitant Coronary Artery Disease (CAD), who were prescribed with Warfarin. From existing data from the Japan Medical Data Vision Co. Ltd. (MDV) database. The study period started on April 18th, 2011 (start of data collection) to December 31st, 2020 (end of data collection).	Rivaroxaban - Matched With Warfarin Using the s-IPTW Method n=20422 Participants Matched cohort of patients with on-valvular atrial fibrillation (NVAF) with concomitant Coronary Artery Disease (CAD), who were prescribed with Rivaroxaban. From existing data from the Japan Medical Data Vision Co. Ltd. (MDV) database. The study period started on April 18th, 2011 (start of data collection) to December 31st, 2020 (end of data collection).	Warfarin - Matched With Rivaroxaban Using the s-IPTW Method n=12231 Participants Matched cohort of patients with on-valvular atrial fibrillation (NVAF) with concomitant Coronary Artery Disease (CAD), who were prescribed with Warfarin. From existing data from the Japan Medical Data Vision Co. Ltd. (MDV) database. The study period started on April 18th, 2011 (start of data collection) to December 31st, 2020 (end of data collection).	Dabigatran - Matched With Rivaroxaban Using the s-IPTW Method n=6682 Participants Matched cohort of patients with on-valvular atrial fibrillation (NVAF) with concomitant Coronary Artery Disease (CAD), who were prescribed with Dabigatran. From existing data from the Japan Medical Data Vision Co. Ltd. (MDV) database. The study period started on April 18th, 2011 (start of data collection) to December 31st, 2020 (end of data collection).	Rivaroxaban - Matched With Dabigatran Using the s-IPTW Method n=20422 Participants Matched cohort of patients with on-valvular atrial fibrillation (NVAF) with concomitant Coronary Artery Disease (CAD), who were prescribed with Rivaroxaban. From existing data from the Japan Medical Data Vision Co. Ltd. (MDV) database. The study period started on April 18th, 2011 (start of data collection) to December 31st, 2020 (end of data collection)
Incidence Rate of Fatal or Non-fatal Major Bleeding	26 Events per 1,000 person-years Interval 22.0 to 31.0	52 Events per 1,000 person-years Interval 47.0 to 57.0	41 Events per 1,000 person-years Interval 38.0 to 44.0	52 Events per 1,000 person-years Interval 47.0 to 57.0	26 Events per 1,000 person-years Interval 22.0 to 31.0	41 Events per 1,000 person-years Interval 38.0 to 44.0

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Dabigatran - Matched With Warfarin Using the s-IPTW Method n=6682 Participants Matched cohort of patients with on-valvular atrial fibrillation (NVAF) with concomitant Coronary Artery Disease (CAD), who were prescribed with Dabigatran. From existing data from the Japan Medical Data Vision Co. Ltd. (MDV) database. The study period started on April 18th, 2011 (start of data collection) to December 31st, 2020 (end of data collection).	Warfarin - Matched With Dabigatran Using the s-IPTW Method n=12231 Participants Matched cohort of patients with on-valvular atrial fibrillation (NVAF) with concomitant Coronary Artery Disease (CAD), who were prescribed with Warfarin. From existing data from the Japan Medical Data Vision Co. Ltd. (MDV) database. The study period started on April 18th, 2011 (start of data collection) to December 31st, 2020 (end of data collection).	Rivaroxaban - Matched With Warfarin Using the s-IPTW Method n=20422 Participants Matched cohort of patients with on-valvular atrial fibrillation (NVAF) with concomitant Coronary Artery Disease (CAD), who were prescribed with Rivaroxaban. From existing data from the Japan Medical Data Vision Co. Ltd. (MDV) database. The study period started on April 18th, 2011 (start of data collection) to December 31st, 2020 (end of data collection).	Warfarin - Matched With Rivaroxaban Using the s-IPTW Method n=12231 Participants Matched cohort of patients with on-valvular atrial fibrillation (NVAF) with concomitant Coronary Artery Disease (CAD), who were prescribed with Warfarin. From existing data from the Japan Medical Data Vision Co. Ltd. (MDV) database. The study period started on April 18th, 2011 (start of data collection) to December 31st, 2020 (end of data collection).	Dabigatran - Matched With Rivaroxaban Using the s-IPTW Method n=6682 Participants Matched cohort of patients with on-valvular atrial fibrillation (NVAF) with concomitant Coronary Artery Disease (CAD), who were prescribed with Dabigatran. From existing data from the Japan Medical Data Vision Co. Ltd. (MDV) database. The study period started on April 18th, 2011 (start of data collection) to December 31st, 2020 (end of data collection).	Rivaroxaban - Matched With Dabigatran Using the s-IPTW Method n=20422 Participants Matched cohort of patients with on-valvular atrial fibrillation (NVAF) with concomitant Coronary Artery Disease (CAD), who were prescribed with Rivaroxaban. From existing data from the Japan Medical Data Vision Co. Ltd. (MDV) database. The study period started on April 18th, 2011 (start of data collection) to December 31st, 2020 (end of data collection)
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 Interval 200.0 to 228.0	275 Events per 1,000 person-years Interval 264.0 to 288.0	228 Events per 1,000 person-years Interval 220.0 to 237.0	275 Events per 1,000 person-years Interval 264.0 to 288.0	213 Events per 1,000 person-years Interval 200.0 to 228.0	228 Events per 1,000 person-years Interval 220.0 to 237.0

Adverse Events

Warfarin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Dabigatran

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Rivaroxaban

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place