Trial Outcomes & Findings for Drug Persistence/Adherence in Patients Treated With Dabigatran or VKA for Stroke Prevention in Non Valvular Atrial Fibrillation (SPAF) (NCT NCT02240667)

Last Updated: 2019-04-19

Results Overview

Percentage of patients treated with the initially allocated anticoagulant at the 12-month visit, defined as Kaplan Meier estimate at 12 months for persistence, stratified for dabigatran etexilate and VKA.Persistence is defined as the time between initiation and permanent discontinuation of therapy. The initiation date is the documented start of treatment (at visit 1), and the date of permanent discontinuation is the documented permanent discontinuation of dabigatran etexilate or VKA therapy.

Recruitment status

COMPLETED

Target enrollment

1506 participants

Primary outcome timeframe

12 month (Visit 5)

Results posted on

2019-04-19

Participant Flow

In this study 1506 patients were entered, 1421 patients had at least one documented prescription of dabigatran etexilate (DE) or vitamin K antagonists (VKA)and were analyzed in the Treated set. 952 patients were matched 1:1 based on Propensity Score (PS).

The patients were enrolled from 1000 sites from Germany. Approximately 2/3 (about 670) will be community-based primary care internists/general practitioners and approximately 1/3 (about 330) community-based cardiologists across Germany.

Participant milestones

Participant milestones
Measure	Dabigatran (Dabigatran vs VKA) Patients with non-valvular AF treated with Dabigatran as the first Oral Anticoagulants (OACs) for stroke prevention.	Vitamin K Antagonists (VKA) Patients with non-valvular AF treated with VKA as the first Oral Anticoagulants (OACs) for stroke prevention.
Overall Study STARTED	771	650
Overall Study COMPLETED	771	650
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dabigatran (Dabigatran vs VKA) n=771 Participants Patients with non-valvular AF treated with Dabigatran as the first Oral Anticoagulants (OACs) for stroke prevention.	Vitamin K Antagonists (VKA) n=650 Participants Patients with non-valvular AF treated with VKA as the first Oral Anticoagulants (OACs) for stroke prevention.	Total n=1421 Participants Total of all reporting groups
Age, Continuous Overall	75 Years n=771 Participants • TS	75 Years n=650 Participants • TS	75 Years n=1421 Participants • TS
Age, Continuous Dabigatran vs VKA(matched pop)	75 Years n=476 Participants • TS	75 Years n=476 Participants • TS	75 Years n=952 Participants • TS
Sex: Female, Male Overall · Female	339 Participants n=771 Participants • TS	284 Participants n=650 Participants • TS	623 Participants n=1421 Participants • TS
Sex: Female, Male Overall · Male	432 Participants n=771 Participants • TS	366 Participants n=650 Participants • TS	798 Participants n=1421 Participants • TS
Sex: Female, Male Dabigatran vs VKA(matched pop) · Female	214 Participants n=476 Participants • TS	205 Participants n=476 Participants • TS	419 Participants n=952 Participants • TS
Sex: Female, Male Dabigatran vs VKA(matched pop) · Male	262 Participants n=476 Participants • TS	271 Participants n=476 Participants • TS	533 Participants n=952 Participants • TS
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: 12 month (Visit 5)

Population: Patients in the TS who were matched 1:1 based on propensity score matching in order to ensure comparability of outcome variables between both treatment groups (dabigatran etexilate and VKA).

Outcome measures

Outcome measures
Measure	Dabigatran (Dabigatran vs VKA) n=476 Participants Patients with non-valvular AF treated with dabigatran as the first Oral Anticoagulants (OACs) were matched 1:1 based on Propensity Score (PS).	VKA (Dabigatran vs VKA) n=476 Participants Patients with non-valvular AF treated with VKA as the first Oral Anticoagulants (OACs) were matched 1:1 based on Propensity Score (PS).
Percentage of Patients Treated With Anticoagulation Initially Started at the 12 Month	89.5 percentage of participants Interval 86.3 to 91.9	89.5 percentage of participants Interval 86.3 to 92.0

SECONDARY outcome

Timeframe: 6 month (visit 3)

Percentage of patients with low, medium or high adherence at the 6-month visit, stratified for dabigatran etexilate and VKA; categorisation is done on the basis of the Morisky questionnaire (high, medium and low adherence with a Morisky score of 0, 1 to 2, and \> 2, respectively).

Outcome measures

Outcome measures
Measure	Dabigatran (Dabigatran vs VKA) n=476 Participants Patients with non-valvular AF treated with dabigatran as the first Oral Anticoagulants (OACs) were matched 1:1 based on Propensity Score (PS).	VKA (Dabigatran vs VKA) n=476 Participants Patients with non-valvular AF treated with VKA as the first Oral Anticoagulants (OACs) were matched 1:1 based on Propensity Score (PS).
Percentage of Patients With Low, Medium or High Adherence at the Timepoint of 6 Months-visit. Low	19.12 Percentage of participants	23.74 Percentage of participants
Percentage of Patients With Low, Medium or High Adherence at the Timepoint of 6 Months-visit. Medium	45.8 Percentage of participants	46.85 Percentage of participants
Percentage of Patients With Low, Medium or High Adherence at the Timepoint of 6 Months-visit. High	5.88 Percentage of participants	3.99 Percentage of participants
Percentage of Patients With Low, Medium or High Adherence at the Timepoint of 6 Months-visit. Missing	29.2 Percentage of participants	25.42 Percentage of participants

SECONDARY outcome

Timeframe: Visit 2, 3, 4 and 5 (after approx. 3, 6, 9 and 12 months of treatment)

Number of patients with the reason for definitive treatment discontinuation

Outcome measures

Outcome measures
Measure	Dabigatran (Dabigatran vs VKA) n=476 Participants Patients with non-valvular AF treated with dabigatran as the first Oral Anticoagulants (OACs) were matched 1:1 based on Propensity Score (PS).	VKA (Dabigatran vs VKA) n=476 Participants Patients with non-valvular AF treated with VKA as the first Oral Anticoagulants (OACs) were matched 1:1 based on Propensity Score (PS).
Number of Patients With the Reason for Definitive Treatment Discontinuation Visit 2 (Month 3) · Serious adverse event	0 Participants	0 Participants
Number of Patients With the Reason for Definitive Treatment Discontinuation Visit 2 (Month 3) · Patient's wish	1 Participants	1 Participants
Number of Patients With the Reason for Definitive Treatment Discontinuation Visit 2 (Month 3) · Decision of physician	1 Participants	0 Participants
Number of Patients With the Reason for Definitive Treatment Discontinuation Visit 2 (Month 3) · Other	0 Participants	1 Participants
Number of Patients With the Reason for Definitive Treatment Discontinuation Visit 3 (Month 6) · Serious adverse event	1 Participants	1 Participants
Number of Patients With the Reason for Definitive Treatment Discontinuation Visit 3 (Month 6) · Patient's wish	0 Participants	1 Participants
Number of Patients With the Reason for Definitive Treatment Discontinuation Visit 3 (Month 6) · Decision of physician	1 Participants	1 Participants
Number of Patients With the Reason for Definitive Treatment Discontinuation Visit 3 (Month 6) · Other	1 Participants	1 Participants
Number of Patients With the Reason for Definitive Treatment Discontinuation Visit 4 (Month 9) · Serious adverse event	0 Participants	0 Participants
Number of Patients With the Reason for Definitive Treatment Discontinuation Visit 4 (Month 9) · Patient's wish	0 Participants	0 Participants
Number of Patients With the Reason for Definitive Treatment Discontinuation Visit 4 (Month 9) · Decision of physician	0 Participants	2 Participants
Number of Patients With the Reason for Definitive Treatment Discontinuation Visit 4 (Month 9) · Other	0 Participants	1 Participants
Number of Patients With the Reason for Definitive Treatment Discontinuation Visit 5 (Month 12) · Serious adverse event	0 Participants	0 Participants
Number of Patients With the Reason for Definitive Treatment Discontinuation Visit 5 (Month 12) · Patient's wish	1 Participants	0 Participants
Number of Patients With the Reason for Definitive Treatment Discontinuation Visit 5 (Month 12) · Decision of physician	0 Participants	2 Participants
Number of Patients With the Reason for Definitive Treatment Discontinuation Visit 5 (Month 12) · Other	2 Participants	0 Participants

Adverse Events

Dabigatran (Dabigatran vs VKA)

Serious events: 45 serious events

Other events: 0 other events

Deaths: 10 deaths

Vitamin K Antagonists (VKA)

Serious events: 39 serious events

Other events: 0 other events

Deaths: 5 deaths

Serious adverse events

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 Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Dabigatran (Dabigatran vs VKA) n=771 participants at risk Patients with non-valvular AF treated with Dabigatran as the first Oral Anticoagulants (OACs) for stroke prevention.	Vitamin K Antagonists (VKA) n=650 participants at risk Patients with non-valvular AF treated with VKA as the first Oral Anticoagulants (OACs) for stroke prevention.
Cardiac disorders Bradycardia	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Cardiac disorders Left ventricular dysfunction	0.00% 0/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.15% 1/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Ear and labyrinth disorders Vertigo	0.26% 2/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Cardiac disorders Cardiac failure	0.52% 4/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.77% 5/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Cardiac disorders Atrial fibrillation	0.26% 2/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.46% 3/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Cardiac disorders Acute coronary syndrome	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.62% 4/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Cardiac disorders Cardiac arrest	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.46% 3/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Cardiac disorders Angina pectoris	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.31% 2/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Cardiac disorders Myocardial infarction	0.26% 2/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.15% 1/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Cardiac disorders Ventricular fibrillation	0.26% 2/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Cardiac disorders Atrial tachycardia	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Cardiac disorders Mitral valve disease	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Eye disorders Optic ischaemic neuropathy	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Gastrointestinal disorders Vomiting	0.26% 2/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.15% 1/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Gastrointestinal disorders Ileus	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.15% 1/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Gastrointestinal disorders Gastric haemorrhage	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.15% 1/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Gastrointestinal disorders Oesophageal ulcer	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Gastrointestinal disorders Abdominal pain upper	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Gastrointestinal disorders Large intestinal haemorrhage	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Gastrointestinal disorders Diarrhoea	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Gastrointestinal disorders Gastrointestinal pain	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Gastrointestinal disorders Intestinal ischaemia	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Gastrointestinal disorders Nausea	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Gastrointestinal disorders Duodenal perforation	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Gastrointestinal disorders Rectal haemorrhage	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Gastrointestinal disorders Anal haemorrhage	0.00% 0/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.15% 1/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Gastrointestinal disorders Pancreatitis	0.00% 0/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.15% 1/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Gastrointestinal disorders Papilla of Vater stenosis	0.00% 0/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.15% 1/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
General disorders Multiple organ dysfunction syndrome	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
General disorders Generalised oedema	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Hepatobiliary disorders Cholestasis	0.00% 0/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.15% 1/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Hepatobiliary disorders Jaundice	0.00% 0/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.15% 1/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Hepatobiliary disorders Cholecystitis	0.00% 0/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.15% 1/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Immune system disorders Hypersensitivity	0.00% 0/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.15% 1/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Infections and infestations Sepsis	0.39% 3/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Infections and infestations Lung infection	0.26% 2/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.15% 1/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Infections and infestations Wound infection	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.15% 1/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Infections and infestations Bronchitis	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.15% 1/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Infections and infestations Paronychia	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.
Infections and infestations Urinary tract infection	0.13% 1/771 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.	0.00% 0/650 • From start of treatment until six days after permanent treatment discontinuation or end of study, up to 12 months. The Treated set (TS) includes all patients with main diagnosis of nonvalvular AF with at least one evaluable efficacy endpoint (being on treatment is an efficacy endpoint). Treatment emergent Adverse events were reported.