Atrial Fibrillation, Stroke
Conditions
Brief summary
In this part of the Registry Program patients with non-valvular atrial fibrillation (AF) at risk for stroke are enrolled to characterize the target population and to collect real world data on important outcome events. For administrative purposes the study is divided into two protocol numbers: 1160.129 for all non-EU (European Union) and non-EEA (European Economic Area) countries, and 1160.136 for EU and EEA countries. The total number of patients enrolled in both protocols is estimated to be 48,000 patients, and all these patients will be included in the data analysis for study 1160.129.
Interventions
None listed
Sponsors
Boehringer Ingelheim
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age =\>18 years at enrollment 2. Male or female patient (or legally acceptable representative) willing and able to provide written informed consent 3. Patient newly diagnosed (\< 3 months prior to baseline visit) with non-valvular AF and at risk for stroke. Other inclusion criteria apply.
Exclusion criteria
1. Presence of any mechanical heart valve, or valve disease that is expected to require valve replacement intervention; 2. Patients who have received more than 60 days of vitamin K antagonist (VKA) treatment in their lifetime; 3. AF with a generally reversible cause; 4. Patients with a medical condition other than atrial fibrillation for which chronic use of an oral anticoagulant (for example, a VKA) is indicated Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate of Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction, Life-threatening Bleeding Events and Vascular Death) - Phase II | From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years. | Incidence rate of composite outcome which includes events of Stroke, systemic embolism, myocardial infarction, life-threatening bleeding events and vascular death on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only. In case of multiple events for a patient, the first event was considered. |
| Incidence Rate of Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction, Life-threatening Bleeding Events and Vascular Death) - Phase III | From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years. | Incidence rate of composite outcome which includes events of Stroke, systemic embolism, myocardial infarction, life-threatening bleeding events and vascular death on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. In case of multiple events for a patient, the first event was considered. Unknown cause of death was imputed by multiple imputation. Counts were based on the average of the 20 restricted data sets. The average of the 20 incidence rates from the 20 imputed datasets were used to obtain the point estimate of the incidence rate that is reported here. The bootstrapping approach was used to obtain the 95% confidence interval of the incidence rate. |
| Incidence Rate of Systemic Embolism (SE) - Phase III | From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years. | Incidence rate of systemic embolism (SE) on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. |
| Incidence Rate of Vascular Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction and Vascular Death) - Phase II | From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years. | Incidence rate of vascular composite outcome including events of stroke, systemic embolism, myocardial infarction and vascular death on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only. In case of multiple events for a patient, the first event was considered. |
| Incidence Rate of Vascular Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction and Vascular Death) - Phase III | From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years. | Incidence rate of vascular composite outcome including events of stroke, systemic embolism, myocardial infarction and vascular death on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. In case of multiple events for a patient, the first event was considered. Unknown death was imputed by multiple imputation. Counts were based on the average of the 20 restricted data sets. The average of the 20 incidence rates from the 20 imputed datasets were used to obtain the point estimate of the incidence rate that is reported here. The bootstrapping approach was used to obtain the 95% confidence interval of the incidence rate. |
| Incidence Rate of Stroke or Systemic Embolism - Phase III | From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years. | Incidence rate of stroke or systemic embolism on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. |
| Incidence Rate of Stroke - Phase II | From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years. | Incidence rate of stroke on all eligible patients excluding prescribed but not taken set for Dabigatran etexilate (DE) of phase II only is presented. Stroke is an acute onset of a focal neurological deficit of presumed vascular origin lasting for 24 hours or more or resulting in death. The stroke included ischemic or hemorrhagic or uncertain classification. |
| Incidence Rate of Stroke - Phase III | From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years. | Incidence rate of stroke on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. Stroke is an acute onset of a focal neurological deficit of presumed vascular origin lasting for 24 hours or more or resulting in death. The stroke included ischemic or hemorrhagic or uncertain classification. |
| Incidence Rate of Transient Ischaemic Attack (TIA) - Phase II | From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years. | Incidence rate of transient ischaemic attack (TIA) on on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented. |
| Incidence Rate of Transient Ischaemic Attack (TIA) - Phase III | From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years. | Incidence rate of transient ischaemic attack (TIA) on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. |
| Incidence Rate of Systemic Embolism (SE) - Phase II | From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years. | Incidence rate of systemic embolism (SE) on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented. |
| Incidence Rate of Pulmonary Embolism (PE) - Phase II | From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years. | Incidence rate of pulmonary embolism (PE) on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented. |
| Incidence Rate of Pulmonary Embolism (PE) - Phase III | From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years. | Incidence rate of pulmonary embolism (PE) on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. |
| Incidence Rate of Major Bleeding Events (MBE) - Phase II | From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years. | Incidence rate of major bleeding events (MBE) on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented. Major bleeding was defined as meeting one or more of the following criteria: Overt bleeding associated with a reduction in haemoglobin of at least 20 grams per liter or leading to a transfusion of at least 2 units of blood or packed cells; Symptomatic bleeding in a critical area or organ: Intraocular, intracranial, intraspinal or intramuscular with compartment syndrome, retroperitoneal bleeding, intra-articular bleeding or pericardial bleeding; Life-threatening bleeding. |
| Incidence Rate of Major Bleeding Events (MBE) - Phase III | From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years. | Incidence rate of major bleeding events on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. Major bleeding was defined as meeting one or more of the following criteria: Overt bleeding associated with a reduction in haemoglobin of at least 20 grams per liter or leading to a transfusion of at least 2 units of blood or packed cells; Symptomatic bleeding in a critical area or organ: Intraocular, intracranial, intraspinal or intramuscular with compartment syndrome, retroperitoneal bleeding, intra-articular bleeding or pericardial bleeding; Life-threatening bleeding. |
| Incidence Rate of Life-threatening Bleeding Events - Phase II | From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years. | Incidence rate of life-threatening bleeding events on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented. Life-threatening bleeding was defined as meeting one or more of the following criteria: Symptomatic intracranial bleed; Reduction in haemoglobin of at least 50 grams per liter; Transfusion of at least 4 units of blood or packed cells, associated with hypotension requiring the use of intravenous inotropic agents; Necessitated surgical intervention; Fatal bleeding. |
| Incidence Rate of Life-threatening Bleeding Events - Phase III | From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years. | Incidence rate of life-threatening bleeding events on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. Life-threatening bleeding was defined as meeting one or more of the following criteria: Symptomatic intracranial bleed; Reduction in haemoglobin of at least 50 grams per liter; Transfusion of at least 4 units of blood or packed cells, associated with hypotension requiring the use of intravenous inotropic agents; Necessitated surgical intervention; Fatal bleeding. |
| Incidence Rate of Myocardial Infarction (MI) - Phase II | From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years. | Incidence rate of myocardial infarction (MI) on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented. |
| Incidence Rate of Myocardial Infarction (MI) - Phase III | From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years. | Incidence rate of myocardial infarction on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. |
| Incidence Rate of All-cause Death - Phase II | From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years. | Incidence rate of all-cause death on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented. |
| Incidence Rate of All-cause Death - Phase III | From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years. | Incidence rate of all-cause death on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. |
| Incidence Rate of Vascular Death - Phase II | From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years. | Incidence rate of vascular death on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented. |
| Incidence Rate of Vascular Death - Phase III | From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years. | Incidence rate of vascular death on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. |
Countries
Argentina, Brazil, Canada, Chile, China, Colombia, Ecuador, Hong Kong, Japan, Lebanon, Mexico, Peru, Russia, Saudi Arabia, Singapore, South Africa, South Korea, Taiwan, United Arab Emirates, United States, Venezuela
Participant flow
Recruitment details
GLORIA-AF was an international, multicentre, non-interventional study based on prospectively collected data for patients (pts) with newly diagnosed non-valvular atrial fibrillation (NVAF). In Ph II, pts baseline characteristics (BC), their antithrombotic treatment patterns and outcomes with 2 years of follow-up for dabigatran alone were collected prospectively. Ph III collected prospective data on pts BC, their treatments and outcomes with 3 years of follow-up for all pts in real-world setting.
Pre-assignment details
All patients were screened for eligibility prior to participation in the study. Patients attended a participating site which ensured that they (the patients) strictly met all inclusion and none of the exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Dabigatran Etexilate - Baseline (Phase II) Patients who were prescribed Dabigatran etexilate at baseline of Phase II were included in this group. Patients could take other Antithrombotic treatments later during the study.
Patients who were newly diagnosed non-valvular Atrial Fibrillation (AF) less than 3 months before the baseline visits (less than 4.5 months before baseline visit for Latin America) and who were at risk for stroke in a real-life setting. Antithrombotic treatments were used according to local practice for stroke prevention. The choice of antithrombotic agent and dosing was at the discretion of the treating physician. | 4,873 |
| Vitamin K Antagonist (VKA) - Baseline (Phase II) Patients who were prescribed Vitamin K Antagonist (VKA) at baseline of Phase II were included in this group. Patients could take other Antithrombotic treatments later during the study.
Patients who were newly diagnosed non-valvular Atrial Fibrillation (AF) less than 3 months before the baseline visits (less than 4.5 months before baseline visit for Latin America) and who were at risk for stroke in a real-life setting. Antithrombotic treatments were used according to local practice for stroke prevention. The choice of antithrombotic agent and dosing was at the discretion of the treating physician. | 4,963 |
| Rivaroxaban - Baseline (Phase II) Patients who were prescribed Rivaroxaban at baseline of Phase II were included in this group. Patients could take other Antithrombotic treatments later during the study.
Patients who were newly diagnosed non-valvular Atrial Fibrillation (AF) less than 3 months before the baseline visits (less than 4.5 months before baseline visit for Latin America) and who were at risk for stroke in a real-life setting. Antithrombotic treatments were used according to local practice for stroke prevention. The choice of antithrombotic agent and dosing was at the discretion of the treating physician. | 1,755 |
| Apixaban - Baseline (Phase II) Patients who were prescribed Apixaban at baseline of Phase II were included in this group. Patients could take other Antithrombotic treatments later during the study.
Patients who were newly diagnosed non-valvular Atrial Fibrillation (AF) less than 3 months before the baseline visits (less than 4.5 months before baseline visit for Latin America) and who were at risk for stroke in a real-life setting. Antithrombotic treatments were used according to local practice for stroke prevention. The choice of antithrombotic agent and dosing was at the discretion of the treating physician. | 703 |
| Acetylsalicylic Acid (ASA) - Baseline (Phase II) Patients who were prescribed Acetylsalicylic acid (ASA) at baseline of Phase II were included in this group. Patients could take other Antithrombotic treatments later during the study.
Patients who were newly diagnosed non-valvular Atrial Fibrillation (AF) less than 3 months before the baseline visits (less than 4.5 months before baseline visit for Latin America) and who were at risk for stroke in a real-life setting. Antithrombotic treatments were used according to local practice for stroke prevention. The choice of antithrombotic agent and dosing was at the discretion of the treating physician. | 1,714 |
| Antiplts Other Than ASA - Baseline (Phase II) Patients who were prescribed Antiplts other than Acetylsalicylic acid (ASA) at baseline of Phase II were included in this group. Patients could take other Antithrombotic treatments later during the study.
Patients who were newly diagnosed non-valvular Atrial Fibrillation (AF) less than 3 months before the baseline visits (less than 4.5 months before baseline visit for Latin America) and who were at risk for stroke in a real-life setting. Antithrombotic treatments were used according to local practice for stroke prevention. The choice of antithrombotic agent and dosing was at the discretion of the treating physician. | 126 |
| No Treatment - Baseline (Phase II) Patients who were not prescribed any antithrombotic treatments at baseline of Phase II were included in this group. Patients could take other Antithrombotic treatments later during the study.
Patients who were newly diagnosed non-valvular Atrial Fibrillation (AF) less than 3 months before the baseline visits (less than 4.5 months before baseline visit for Latin America) and who were at risk for stroke in a real-life setting. Antithrombotic treatments were used according to local practice for stroke prevention. The choice of antithrombotic agent and dosing was at the discretion of the treating physician. | 1,170 |
| Combinations With Oral Anticoagulants - Baseline (Phase II) Patients who were prescribed combinations with oral anticoagulants treatments at baseline of Phase II were included in this group. Patients in this group were not included in the safety analysis as no specific treatment can be defined.
Patients who were newly diagnosed non-valvular Atrial Fibrillation (AF) less than 3 months before the baseline visits (less than 4.5 months before baseline visit for Latin America) and who were at risk for stroke in a real-life setting. Antithrombotic treatments were used according to local practice for stroke prevention. The choice of antithrombotic agent and dosing was at the discretion of the treating physician. | 4 |
| Dabigatran Etexilate - Baseline (Phase III) Patients who were prescribed Dabigatran etexilate at baseline of Phase III were included in this group. Patients could take other Antithrombotic treatments later during the study.
Patients who were newly diagnosed non-valvular Atrial Fibrillation (AF) less than 3 months before the baseline visits (less than 4.5 months before baseline visit for Latin America) and who were at risk for stroke in a real-life setting. Antithrombotic treatments were used according to local practice for stroke prevention. The choice of antithrombotic agent and dosing was at the discretion of the treating physician. | 3,839 |
| Vitamin K Antagonist (VKA) - Baseline (Phase III) Patients who were prescribed Vitamin K Antagonist (VKA) at baseline of Phase III were included in this group. Patients could take other Antithrombotic treatments later during the study.
Patients who were newly diagnosed non-valvular Atrial Fibrillation (AF) less than 3 months before the baseline visits (less than 4.5 months before baseline visit for Latin America) and who were at risk for stroke in a real-life setting. Antithrombotic treatments were used according to local practice for stroke prevention. The choice of antithrombotic agent and dosing was at the discretion of the treating physician. | 4,836 |
| Rivaroxaban - Baseline (Phase III) Patients who were prescribed Rivaroxaban at baseline of Phase III were included in this group. Patients could take other Antithrombotic treatments later during the study.
Patients who were newly diagnosed non-valvular Atrial Fibrillation (AF) less than 3 months before the baseline visits (less than 4.5 months before baseline visit for Latin America) and who were at risk for stroke in a real-life setting. Antithrombotic treatments were used according to local practice for stroke prevention. The choice of antithrombotic agent and dosing was at the discretion of the treating physician. | 4,015 |
| Apixaban - Baseline (Phase III) Patients who were prescribed Apixaban at baseline of Phase III were included in this group. Patients could take other Antithrombotic treatments later during the study.
Patients who were newly diagnosed non-valvular Atrial Fibrillation (AF) less than 3 months before the baseline visits (less than 4.5 months before baseline visit for Latin America) and who were at risk for stroke in a real-life setting. Antithrombotic treatments were used according to local practice for stroke prevention. The choice of antithrombotic agent and dosing was at the discretion of the treating physician. | 4,505 |
| Edoxaban - Baseline (Phase III) Patients who were prescribed Edoxaban at baseline of Phase III were included in this group. Patients could take other Antithrombotic treatments later during the study.
Patients who were newly diagnosed non-valvular Atrial Fibrillation (AF) less than 3 months before the baseline visits (less than 4.5 months before baseline visit for Latin America) and who were at risk for stroke in a real-life setting. Antithrombotic treatments were used according to local practice for stroke prevention. The choice of antithrombotic agent and dosing was at the discretion of the treating physician. | 332 |
| Acetylsalicylic Acid (ASA) - Baseline (Phase III) Patients who were prescribed Acetylsalicylic acid (ASA) at baseline of Phase III were included in this group. Patients could take other Antithrombotic treatments later during the study.
Patients who were newly diagnosed non-valvular Atrial Fibrillation (AF) less than 3 months before the baseline visits (less than 4.5 months before baseline visit for Latin America) and who were at risk for stroke in a real-life setting. Antithrombotic treatments were used according to local practice for stroke prevention. The choice of antithrombotic agent and dosing was at the discretion of the treating physician. | 2,163 |
| Antiplts Other Than ASA - Baseline (Phase III) Patients who were prescribed Antiplatelets other than ASA at baseline of Phase III were included in this group. Patients could take other Antithrombotic treatments later during the study.
Patients who were newly diagnosed non-valvular Atrial Fibrillation (AF) less than 3 months before the baseline visits (less than 4.5 months before baseline visit for Latin America) and who were at risk for stroke in a real-life setting. Antithrombotic treatments may be used according to local practice for stroke prevention. The choice of antithrombotic agent and dosing was at the discretion of the treating physician. | 213 |
| No Treatment - Baseline (Phase III) Patients who were not prescribed any antithrombotic treatments at baseline of Phase III were included in this group. Patients could take other Antithrombotic treatments later during the study.
Patients who were newly diagnosed non-valvular Atrial Fibrillation (AF) less than 3 months before the baseline visits (less than 4.5 months before baseline visit for Latin America) and who were at risk for stroke in a real-life setting. Antithrombotic treatments were used according to local practice for stroke prevention. The choice of antithrombotic agent and dosing was at the discretion of the treating physician. | 1,386 |
| Combinations With Oral Anticoagulants - Baseline (Phase III) Patients who were prescribed combinations with oral anticoagulants treatments at baseline of Phase III were included in this group. Patients in this group were not included in the safety analysis as no specific treatment can be defined.
Patients who were newly diagnosed non-valvular Atrial Fibrillation (AF) less than 3 months before the baseline visits (less than 4.5 months before baseline visit for Latin America) and who were at risk for stroke in a real-life setting. Antithrombotic treatments were used according to local practice for stroke prevention. The choice of antithrombotic agent and dosing was at the discretion of the treating physician. | 11 |
| Total | 36,608 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 306 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 215 | 309 | 224 | 212 | 11 | 164 | 17 | 127 | 1 |
| Overall Study | No end of study case report form | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 1 | 2 | 3 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Not being followed up | 0 | 4,963 | 1,755 | 703 | 1,714 | 126 | 1,170 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Not eligible | 91 | 140 | 29 | 12 | 22 | 2 | 39 | 1 | 40 | 126 | 39 | 33 | 1 | 19 | 1 | 32 | 0 |
| Overall Study | Other reasons than listed | 437 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 318 | 658 | 433 | 504 | 28 | 239 | 39 | 172 | 0 |
| Overall Study | Withdrawal by Subject | 165 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 83 | 88 | 100 | 114 | 9 | 47 | 6 | 31 | 0 |
Baseline characteristics
| Characteristic | Dabigatran Etexilate - Baseline (Phase II) | Vitamin K Antagonist (VKA) - Baseline (Phase II) | Rivaroxaban - Baseline (Phase II) | Apixaban - Baseline (Phase II) | Acetylsalicylic Acid (ASA) - Baseline (Phase II) | Antiplts Other Than ASA - Baseline (Phase II) | No Treatment - Baseline (Phase II) | Combinations With Oral Anticoagulants - Baseline (Phase II) | Dabigatran Etexilate - Baseline (Phase III) | Vitamin K Antagonist (VKA) - Baseline (Phase III) | Rivaroxaban - Baseline (Phase III) | Apixaban - Baseline (Phase III) | Edoxaban - Baseline (Phase III) | Acetylsalicylic Acid (ASA) - Baseline (Phase III) | Antiplts Other Than ASA - Baseline (Phase III) | No Treatment - Baseline (Phase III) | Combinations With Oral Anticoagulants - Baseline (Phase III) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 70.2 Years STANDARD_DEVIATION 10.4 | 71.4 Years STANDARD_DEVIATION 10.6 | 71.5 Years STANDARD_DEVIATION 10.6 | 73.8 Years STANDARD_DEVIATION 10 | 67.7 Years STANDARD_DEVIATION 12.4 | 73.5 Years STANDARD_DEVIATION 10.7 | 68.3 Years STANDARD_DEVIATION 12.5 | 76.0 Years STANDARD_DEVIATION 8.3 | 70.1 Years STANDARD_DEVIATION 10.2 | 71.2 Years STANDARD_DEVIATION 10.3 | 70.3 Years STANDARD_DEVIATION 10.2 | 72.4 Years STANDARD_DEVIATION 10.1 | 72.3 Years STANDARD_DEVIATION 9.4 | 68.0 Years STANDARD_DEVIATION 11.8 | 73.1 Years STANDARD_DEVIATION 10.8 | 67.6 Years STANDARD_DEVIATION 12.2 | 70.2 Years STANDARD_DEVIATION 12.1 | 70.5 Years STANDARD_DEVIATION 10.8 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 20 Participants | 14 Participants | 6 Participants | 0 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 27 Participants | 32 Participants | 32 Participants | 21 Participants | 0 Participants | 7 Participants | 2 Participants | 3 Participants | 1 Participants | 170 Participants |
| Race/Ethnicity, Customized Asian | 423 Participants | 797 Participants | 111 Participants | 93 Participants | 694 Participants | 43 Participants | 603 Participants | 0 Participants | 841 Participants | 760 Participants | 381 Participants | 413 Participants | 125 Participants | 916 Participants | 95 Participants | 593 Participants | 8 Participants | 6896 Participants |
| Race/Ethnicity, Customized Black/African American | 40 Participants | 86 Participants | 42 Participants | 14 Participants | 44 Participants | 0 Participants | 23 Participants | 0 Participants | 47 Participants | 85 Participants | 72 Participants | 118 Participants | 2 Participants | 49 Participants | 2 Participants | 23 Participants | 0 Participants | 647 Participants |
| Race/Ethnicity, Customized Missing | 571 Participants | 211 Participants | 151 Participants | 34 Participants | 26 Participants | 3 Participants | 24 Participants | 0 Participants | 259 Participants | 204 Participants | 260 Participants | 345 Participants | 0 Participants | 75 Participants | 3 Participants | 27 Participants | 0 Participants | 2193 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Other Pacific Islander | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 9 Participants |
| Race/Ethnicity, Customized Other | 447 Participants | 262 Participants | 69 Participants | 24 Participants | 82 Participants | 10 Participants | 21 Participants | 0 Participants | 181 Participants | 144 Participants | 144 Participants | 79 Participants | 2 Participants | 57 Participants | 7 Participants | 32 Participants | 0 Participants | 1561 Participants |
| Race/Ethnicity, Customized White | 3372 Participants | 3590 Participants | 1375 Participants | 538 Participants | 863 Participants | 70 Participants | 497 Participants | 4 Participants | 2484 Participants | 3611 Participants | 3126 Participants | 3528 Participants | 203 Participants | 1057 Participants | 104 Participants | 708 Participants | 2 Participants | 25132 Participants |
| Sex: Female, Male Female | 2162 Participants | 2304 Participants | 773 Participants | 338 Participants | 778 Participants | 58 Participants | 553 Participants | 2 Participants | 1718 Participants | 2152 Participants | 1766 Participants | 2104 Participants | 139 Participants | 931 Participants | 92 Participants | 660 Participants | 6 Participants | 16536 Participants |
| Sex: Female, Male Male | 2711 Participants | 2659 Participants | 982 Participants | 365 Participants | 936 Participants | 68 Participants | 617 Participants | 2 Participants | 2121 Participants | 2684 Participants | 2249 Participants | 2401 Participants | 193 Participants | 1232 Participants | 121 Participants | 726 Participants | 5 Participants | 20072 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 184 / 4,943 | 199 / 4,477 | 465 / 5,894 | 292 / 5,177 | 392 / 6,024 | 23 / 686 | 469 / 6,263 | 46 / 780 |
| other Total, other adverse events | 0 / 4,943 | 0 / 4,477 | 0 / 5,894 | 0 / 5,177 | 0 / 6,024 | 0 / 686 | 0 / 6,263 | 0 / 780 |
| serious Total, serious adverse events | 985 / 4,943 | 118 / 4,477 | 296 / 5,894 | 185 / 5,177 | 217 / 6,024 | 16 / 686 | 225 / 6,263 | 19 / 780 |
Outcome results
Primary
Incidence Rate of All-cause Death - Phase II
Incidence rate of all-cause death on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented.
Time frame: From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years.
Population: All eligible patients who were prescribed DE at baseline in phase II excluding prescribed but not taken. All eligible: All patients who were enrolled and eligible (i.e. did not have any important. protocol violation(s) and who met certain data cleaning requirements).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of All-cause Death - Phase II | 2.48 Events per 100 person-years |
Primary
Incidence Rate of All-cause Death - Phase III
Incidence rate of all-cause death on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only.
Time frame: From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years.
Population: Restricted patient set: was defined only for eligible dabigatran and vitamin K antagonist patients (pts) of phase III who were within region of propensity score (PS) overlap excluding pts in non-overlapping tails of PS distribution, using cut-offs at 1.5th percentile of the PS distribution for dab-exposed group, and 98.5th percentile of distribution for VKA-exposed group. Excluding these pts from the tails of PS distribution reduces channeling bias and improves the validity of comparisons.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of All-cause Death - Phase III | 2.16 Events per 100 person-years |
| Vitamin K Antagonist (VKA) - Baseline (Phase III) | Incidence Rate of All-cause Death - Phase III | 3.57 Events per 100 person-years |
Comparison: A multivariable Cox regression model was performed including variables of treatment, age, gender, prior bleed, previous stroke/transient ischaemic attack/systemic embolism, previous myocardial infarction, abnormal kidney function and concomitant antiplatelets use.95% CI: [0.54, 0.8]Regression, Cox
Primary
Incidence Rate of Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction, Life-threatening Bleeding Events and Vascular Death) - Phase II
Incidence rate of composite outcome which includes events of Stroke, systemic embolism, myocardial infarction, life-threatening bleeding events and vascular death on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only. In case of multiple events for a patient, the first event was considered.
Time frame: From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years.
Population: All eligible patients who were prescribed DE at baseline in phase II excluding prescribed but not taken. All eligible: All patients who were enrolled and eligible (i.e. did not have any important. protocol violation(s) and who met certain data cleaning requirements).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction, Life-threatening Bleeding Events and Vascular Death) - Phase II | 2.06 Events per 100 person-years |
Primary
Incidence Rate of Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction, Life-threatening Bleeding Events and Vascular Death) - Phase III
Incidence rate of composite outcome which includes events of Stroke, systemic embolism, myocardial infarction, life-threatening bleeding events and vascular death on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. In case of multiple events for a patient, the first event was considered. Unknown cause of death was imputed by multiple imputation. Counts were based on the average of the 20 restricted data sets. The average of the 20 incidence rates from the 20 imputed datasets were used to obtain the point estimate of the incidence rate that is reported here. The bootstrapping approach was used to obtain the 95% confidence interval of the incidence rate.
Time frame: From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years.
Population: Restricted patient set: was defined only for eligible dabigatran and vitamin K antagonist patients (pts) of phase III who were within region of propensity score (PS) overlap excluding pts in non-overlapping tails of PS distribution, using cut-offs at 1.5th percentile of the PS distribution for dab-exposed group, and 98.5th percentile of distribution for VKA-exposed group. Excluding these pts from the tails of PS distribution reduces channeling bias and improves the validity of comparisons.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction, Life-threatening Bleeding Events and Vascular Death) - Phase III | 2.21 Events per 100 person-years |
| Vitamin K Antagonist (VKA) - Baseline (Phase III) | Incidence Rate of Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction, Life-threatening Bleeding Events and Vascular Death) - Phase III | 3.23 Events per 100 person-years |
Comparison: A multivariable Cox regression model was performed including variables of treatment, age, gender, prior bleed, previous stroke/transient ischaemic attack/systemic embolism, previous myocardial infarction, abnormal kidney function and concomitant antiplatelets use.95% CI: [0.6, 0.9]Regression, Cox
Primary
Incidence Rate of Life-threatening Bleeding Events - Phase II
Incidence rate of life-threatening bleeding events on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented. Life-threatening bleeding was defined as meeting one or more of the following criteria: Symptomatic intracranial bleed; Reduction in haemoglobin of at least 50 grams per liter; Transfusion of at least 4 units of blood or packed cells, associated with hypotension requiring the use of intravenous inotropic agents; Necessitated surgical intervention; Fatal bleeding.
Time frame: From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years.
Population: All eligible patients who were prescribed DE at baseline in phase II excluding prescribed but not taken. All eligible: All patients who were enrolled and eligible (i.e. did not have any important. protocol violation(s) and who met certain data cleaning requirements).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Life-threatening Bleeding Events - Phase II | 0.46 Events per 100 person-years |
Primary
Incidence Rate of Life-threatening Bleeding Events - Phase III
Incidence rate of life-threatening bleeding events on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. Life-threatening bleeding was defined as meeting one or more of the following criteria: Symptomatic intracranial bleed; Reduction in haemoglobin of at least 50 grams per liter; Transfusion of at least 4 units of blood or packed cells, associated with hypotension requiring the use of intravenous inotropic agents; Necessitated surgical intervention; Fatal bleeding.
Time frame: From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years.
Population: Restricted patient set: was defined only for eligible dabigatran and vitamin K antagonist patients (pts) of phase III who were within region of propensity score (PS) overlap excluding pts in non-overlapping tails of PS distribution, using cut-offs at 1.5th percentile of the PS distribution for dab-exposed group, and 98.5th percentile of distribution for VKA-exposed group. Excluding these pts from the tails of PS distribution reduces channeling bias and improves the validity of comparisons.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Life-threatening Bleeding Events - Phase III | 0.47 Events per 100 person-years |
| Vitamin K Antagonist (VKA) - Baseline (Phase III) | Incidence Rate of Life-threatening Bleeding Events - Phase III | 1.07 Events per 100 person-years |
Primary
Incidence Rate of Major Bleeding Events (MBE) - Phase II
Incidence rate of major bleeding events (MBE) on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented. Major bleeding was defined as meeting one or more of the following criteria: Overt bleeding associated with a reduction in haemoglobin of at least 20 grams per liter or leading to a transfusion of at least 2 units of blood or packed cells; Symptomatic bleeding in a critical area or organ: Intraocular, intracranial, intraspinal or intramuscular with compartment syndrome, retroperitoneal bleeding, intra-articular bleeding or pericardial bleeding; Life-threatening bleeding.
Time frame: From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years.
Population: All eligible patients who were prescribed DE at baseline in phase II excluding prescribed but not taken. All eligible: All patients who were enrolled and eligible (i.e. did not have any important. protocol violation(s) and who met certain data cleaning requirements).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Major Bleeding Events (MBE) - Phase II | 0.97 Events per 100 person-years |
Primary
Incidence Rate of Major Bleeding Events (MBE) - Phase III
Incidence rate of major bleeding events on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. Major bleeding was defined as meeting one or more of the following criteria: Overt bleeding associated with a reduction in haemoglobin of at least 20 grams per liter or leading to a transfusion of at least 2 units of blood or packed cells; Symptomatic bleeding in a critical area or organ: Intraocular, intracranial, intraspinal or intramuscular with compartment syndrome, retroperitoneal bleeding, intra-articular bleeding or pericardial bleeding; Life-threatening bleeding.
Time frame: From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years.
Population: Restricted patient set: was defined only for eligible dabigatran and vitamin K antagonist patients (pts) of phase III who were within region of propensity score (PS) overlap excluding pts in non-overlapping tails of PS distribution, using cut-offs at 1.5th percentile of the PS distribution for dab-exposed group, and 98.5th percentile of distribution for VKA-exposed group. Excluding these pts from the tails of PS distribution reduces channeling bias and improves the validity of comparisons.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Major Bleeding Events (MBE) - Phase III | 0.69 Events per 100 person-years |
| Vitamin K Antagonist (VKA) - Baseline (Phase III) | Incidence Rate of Major Bleeding Events (MBE) - Phase III | 1.44 Events per 100 person-years |
Comparison: A multivariable Cox regression model was performed including variables of treatment, age, gender, prior bleed, previous myocardial infarction, abnormal kidney function, concomitant antiplatelets use and concomitant use of drugs related to bleeding.95% CI: [0.38, 0.73]Regression, Cox
Primary
Incidence Rate of Myocardial Infarction (MI) - Phase II
Incidence rate of myocardial infarction (MI) on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented.
Time frame: From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years.
Population: All eligible patients who were prescribed DE at baseline in phase II excluding prescribed but not taken. All eligible: All patients who were enrolled and eligible (i.e. did not have any important. protocol violation(s) and who met certain data cleaning requirements).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Myocardial Infarction (MI) - Phase II | 0.50 Events per 100 person-years |
Primary
Incidence Rate of Myocardial Infarction (MI) - Phase III
Incidence rate of myocardial infarction on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only.
Time frame: From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years.
Population: Restricted patient set: was defined only for eligible dabigatran and vitamin K antagonist patients (pts) of phase III who were within region of propensity score (PS) overlap excluding pts in non-overlapping tails of PS distribution, using cut-offs at 1.5th percentile of the PS distribution for dab-exposed group, and 98.5th percentile of distribution for VKA-exposed group. Excluding these pts from the tails of PS distribution reduces channeling bias and improves the validity of comparisons.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Myocardial Infarction (MI) - Phase III | 0.40 Events per 100 person-years |
| Vitamin K Antagonist (VKA) - Baseline (Phase III) | Incidence Rate of Myocardial Infarction (MI) - Phase III | 0.53 Events per 100 person-years |
Comparison: A multivariable Cox regression model was performed including variables of treatment, age, gender, prior bleed, previous myocardial infarction, concomitant antiplatelets use, concomitant use of drugs related to bleeding, hypertension, and diabetes.95% CI: [0.6, 1.57]Regression, Cox
Primary
Incidence Rate of Pulmonary Embolism (PE) - Phase II
Incidence rate of pulmonary embolism (PE) on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented.
Time frame: From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years.
Population: All eligible patients who were prescribed DE at baseline in phase II excluding prescribed but not taken. All eligible: All patients who were enrolled and eligible (i.e. did not have any important. protocol violation(s) and who met certain data cleaning requirements).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Pulmonary Embolism (PE) - Phase II | 0.07 Events per 100 person-years |
Primary
Incidence Rate of Pulmonary Embolism (PE) - Phase III
Incidence rate of pulmonary embolism (PE) on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only.
Time frame: From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years.
Population: Restricted patient set: was defined only for eligible dabigatran and vitamin K antagonist patients (pts) of phase III who were within region of propensity score (PS) overlap excluding pts in non-overlapping tails of PS distribution, using cut-offs at 1.5th percentile of the PS distribution for dab-exposed group, and 98.5th percentile of distribution for VKA-exposed group. Excluding these pts from the tails of PS distribution reduces channeling bias and improves the validity of comparisons.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Pulmonary Embolism (PE) - Phase III | 0.07 Events per 100 person-years |
| Vitamin K Antagonist (VKA) - Baseline (Phase III) | Incidence Rate of Pulmonary Embolism (PE) - Phase III | 0.06 Events per 100 person-years |
Primary
Incidence Rate of Stroke or Systemic Embolism - Phase III
Incidence rate of stroke or systemic embolism on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only.
Time frame: From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years.
Population: Restricted patient set: was defined only for eligible dabigatran and vitamin K antagonist patients (pts) of phase III who were within region of propensity score (PS) overlap excluding pts in non-overlapping tails of PS distribution, using cut-offs at 1.5th percentile of the PS distribution for dab-exposed group, and 98.5th percentile of distribution for VKA-exposed group. Excluding these pts from the tails of PS distribution reduces channeling bias and improves the validity of comparisons.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Stroke or Systemic Embolism - Phase III | 0.80 Events per 100 person-years |
| Vitamin K Antagonist (VKA) - Baseline (Phase III) | Incidence Rate of Stroke or Systemic Embolism - Phase III | 1.00 Events per 100 person-years |
Comparison: A multivariable Cox regression model was performed including variables of treatment, age, gender, prior bleed, previous stroke/transient ischaemic attack/systemic embolism, previous myocardial infarction, abnormal kidney function and concomitant antiplatelets use.95% CI: [0.57, 1.11]Regression, Cox
Primary
Incidence Rate of Stroke - Phase II
Incidence rate of stroke on all eligible patients excluding prescribed but not taken set for Dabigatran etexilate (DE) of phase II only is presented. Stroke is an acute onset of a focal neurological deficit of presumed vascular origin lasting for 24 hours or more or resulting in death. The stroke included ischemic or hemorrhagic or uncertain classification.
Time frame: From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years.
Population: All eligible patients who were prescribed DE at baseline in phase II excluding prescribed but not taken. All eligible: All patients who were enrolled and eligible (i.e. did not have any important. protocol violation(s) and who met certain data cleaning requirements).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Stroke - Phase II | 0.65 Events per 100 person-years |
Primary
Incidence Rate of Stroke - Phase III
Incidence rate of stroke on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. Stroke is an acute onset of a focal neurological deficit of presumed vascular origin lasting for 24 hours or more or resulting in death. The stroke included ischemic or hemorrhagic or uncertain classification.
Time frame: From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years.
Population: Restricted patient set: was defined only for eligible dabigatran and vitamin K antagonist patients (pts) of phase III who were within region of propensity score (PS) overlap excluding pts in non-overlapping tails of PS distribution, using cut-offs at 1.5th percentile of the PS distribution for dab-exposed group, and 98.5th percentile of distribution for VKA-exposed group. Excluding these pts from the tails of PS distribution reduces channeling bias and improves the validity of comparisons.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Stroke - Phase III | 0.77 Events per 100 person-years |
| Vitamin K Antagonist (VKA) - Baseline (Phase III) | Incidence Rate of Stroke - Phase III | 0.96 Events per 100 person-years |
Comparison: A multivariable Cox regression model was performed including variables of treatment, age, gender, prior bleed, previous stroke/transient ischaemic attack/systemic embolism, previous myocardial infarction, abnormal kidney function and concomitant antiplatelets use.95% CI: [0.57, 1.14]Regression, Cox
Primary
Incidence Rate of Systemic Embolism (SE) - Phase II
Incidence rate of systemic embolism (SE) on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented.
Time frame: From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years.
Population: All eligible patients who were prescribed DE at baseline in phase II excluding prescribed but not taken. All eligible: All patients who were enrolled and eligible (i.e. did not have any important. protocol violation(s) and who met certain data cleaning requirements).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Systemic Embolism (SE) - Phase II | 0.04 Events per 100 person-years |
Primary
Incidence Rate of Systemic Embolism (SE) - Phase III
Incidence rate of systemic embolism (SE) on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only.
Time frame: From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years.
Population: Restricted patient set: was defined only for eligible dabigatran and vitamin K antagonist patients (pts) of phase III who were within region of propensity score (PS) overlap excluding pts in non-overlapping tails of PS distribution, using cut-offs at 1.5th percentile of the PS distribution for dab-exposed group, and 98.5th percentile of distribution for VKA-exposed group. Excluding these pts from the tails of PS distribution reduces channeling bias and improves the validity of comparisons.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Systemic Embolism (SE) - Phase III | 0.04 Events per 100 person-years |
| Vitamin K Antagonist (VKA) - Baseline (Phase III) | Incidence Rate of Systemic Embolism (SE) - Phase III | 0.05 Events per 100 person-years |
Primary
Incidence Rate of Transient Ischaemic Attack (TIA) - Phase II
Incidence rate of transient ischaemic attack (TIA) on on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented.
Time frame: From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years.
Population: All eligible patients who were prescribed DE at baseline in phase II excluding prescribed but not taken. All eligible: All patients who were enrolled and eligible (i.e. did not have any important. protocol violation(s) and who met certain data cleaning requirements).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Transient Ischaemic Attack (TIA) - Phase II | 0.21 Events per 100 person-years |
Primary
Incidence Rate of Transient Ischaemic Attack (TIA) - Phase III
Incidence rate of transient ischaemic attack (TIA) on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only.
Time frame: From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years.
Population: Restricted patient set: was defined only for eligible dabigatran and vitamin K antagonist patients (pts) of phase III who were within region of propensity score (PS) overlap excluding pts in non-overlapping tails of PS distribution, using cut-offs at 1.5th percentile of the PS distribution for dab-exposed group, and 98.5th percentile of distribution for VKA-exposed group. Excluding these pts from the tails of PS distribution reduces channeling bias and improves the validity of comparisons.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Transient Ischaemic Attack (TIA) - Phase III | 0.29 Events per 100 person-years |
| Vitamin K Antagonist (VKA) - Baseline (Phase III) | Incidence Rate of Transient Ischaemic Attack (TIA) - Phase III | 0.32 Events per 100 person-years |
Primary
Incidence Rate of Vascular Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction and Vascular Death) - Phase II
Incidence rate of vascular composite outcome including events of stroke, systemic embolism, myocardial infarction and vascular death on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only. In case of multiple events for a patient, the first event was considered.
Time frame: From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years.
Population: All eligible patients who were prescribed DE at baseline in phase II excluding prescribed but not taken. All eligible: All patients who were enrolled and eligible (i.e. did not have any important. protocol violation(s) and who met certain data cleaning requirements).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Vascular Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction and Vascular Death) - Phase II | 1.74 Events per 100 person-years |
Primary
Incidence Rate of Vascular Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction and Vascular Death) - Phase III
Incidence rate of vascular composite outcome including events of stroke, systemic embolism, myocardial infarction and vascular death on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. In case of multiple events for a patient, the first event was considered. Unknown death was imputed by multiple imputation. Counts were based on the average of the 20 restricted data sets. The average of the 20 incidence rates from the 20 imputed datasets were used to obtain the point estimate of the incidence rate that is reported here. The bootstrapping approach was used to obtain the 95% confidence interval of the incidence rate.
Time frame: From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years.
Population: Restricted patient set: was defined only for eligible dabigatran and vitamin K antagonist patients (pts) of phase III who were within region of propensity score (PS) overlap excluding pts in non-overlapping tails of PS distribution, using cut-offs at 1.5th percentile of the PS distribution for dab-exposed group, and 98.5th percentile of distribution for VKA-exposed group. Excluding these pts from the tails of PS distribution reduces channeling bias and improves the validity of comparisons.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Vascular Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction and Vascular Death) - Phase III | 1.91 Events per 100 person-years |
| Vitamin K Antagonist (VKA) - Baseline (Phase III) | Incidence Rate of Vascular Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction and Vascular Death) - Phase III | 2.62 Events per 100 person-years |
Comparison: A multivariable Cox regression model was performed including variables of treatment, age, gender, prior bleed, previous stroke/transient ischaemic attack/systemic embolism, previous myocardial infarction, abnormal kidney function and concomitant antiplatelets use.95% CI: [0.63, 0.98]Regression, Cox
Primary
Incidence Rate of Vascular Death - Phase II
Incidence rate of vascular death on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented.
Time frame: From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years.
Population: All eligible patients who were prescribed DE at baseline in phase II excluding prescribed but not taken. All eligible: All patients who were enrolled and eligible (i.e. did not have any important. protocol violation(s) and who met certain data cleaning requirements).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Vascular Death - Phase II | 0.85 Events per 100 person-years |
Primary
Incidence Rate of Vascular Death - Phase III
Incidence rate of vascular death on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only.
Time frame: From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years.
Population: Restricted patient set: was defined only for eligible dabigatran and vitamin K antagonist patients (pts) of phase III who were within region of propensity score (PS) overlap excluding pts in non-overlapping tails of PS distribution, using cut-offs at 1.5th percentile of the PS distribution for dab-exposed group, and 98.5th percentile of distribution for VKA-exposed group. Excluding these pts from the tails of PS distribution reduces channeling bias and improves the validity of comparisons.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate - Baseline (Phase II) | Incidence Rate of Vascular Death - Phase III | 0.75 Events per 100 person-years |
| Vitamin K Antagonist (VKA) - Baseline (Phase III) | Incidence Rate of Vascular Death - Phase III | 1.26 Events per 100 person-years |