RELY-ABLE Long Term Multi-center Extension of Dabigatran Treatment in Patients With Atrial Fibrillation Who Completed RE-LY Trial

• Stroke, Annualized Rate of Subjects With Stroke [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]

  Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

  Stroke was an acute onset of a focal neurological deficit of presumed vascular origin lasting for 24 hours or more or resulting in death. The stroke was categorized as ischemic or hemorrhagic or cause unknown based on computerized tomography (CT), magnetic resonance (MR) scanning or autopsy. Fatal stroke was defined as death from any cause within 30 days of stroke. Severity of stroke was assessed by modified Rankin score at discharge from hospital

• Non CNS Systemic Embolism (SEE), Annualized Rate of Subjects With Non-CNS SEE [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]

  Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

  Systemic embolism was an acute vascular occlusion of the extremities or any organ (kidneys, mesenteric arteries, spleen, retina or grafts), and was to be documented by angiography, surgery, scintigraphy, or autopsy.

• Pulmonary Embolism (PE), Annualized Rate of Subjects With PE [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]

  Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

  Pulmonary Embolism was generally documented by one of the following:

  1. an intraluminal filling defect in segmental or more proximal branches on spiral CT scan
  2. an intraluminal filling defect or an extension of an existing defect or a sudden cutoff of vessels more than 2.5 mm in diameter on the pulmonary angiogram
  3. a perfusion defect of at least 75% of a segment with a local normal ventilation result (high-probability) on ventilation/perfusion lung scan (VPLS)
  4. inconclusive spiral CT, pulmonary angiography or lung scintigraphy with demonstration of DVT in the lower extremities by compression ultrasound or venography.
• Acute Myocardial Infarction (MI), Annualized Rate of Subjects With MI [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]

  Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

  a. In subjects not undergoing PCI or CABG a subject should have fulfilled at least 2 of the following: i. Typical prolonged severe chest pain or related symptoms or signs suggestive of MI. ii. Elevation of troponin or CK-MB to more than upper level of normal (ULN) or, if CK-MB was elevated at baseline, re-elevation to more than 50% increase above the previous level. iii. Development of significant Q-waves in at least 2 adjacent ECG leads. b. After percutaneous coronary intervention (within 24h). c. After coronary artery bypass grafting (within 72h). d. Silent myocardial infarction. e. Myocardial infarction could also have been demonstrated at autopsy.

• Deep Vein Thrombosis, Annualized Rate of Subjects With DVT [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]

  Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

  Deep Vein Thrombosis (DVT) was generally documented by one of the following:

  1. abnormal compression ultrasound (CUS),
  2. an intraluminal filling defect on venography.
• Death, Annualized Rate of Subject Death [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]

  Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

  Deaths were classified as being vascular (sudden/arrhythmic, pump failure death, or other vascular, including bleeding) or non-vascular, due to other specified causes (e.g., malignancy), or of unknown etiology.

• Annualized Rate of Subjects With Composite Incidence of Stroke, Non CNS Systemic Embolism (SEE) [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]
  Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.
• Annualized Rate of Subjects With Composite Incidence of Stroke, Non CNS Systemic Embolism (SEE) and All Cause Death [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]
  Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.
• Annualized Rate of Subjects With Composite Incidence of Stroke, Non CNS Systemic Embolism (SEE), Pulmonary Embolism (PE), Myocardial Infarction, Vascular Death [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]
  Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.
• Annualized Rate of Subjects With Composite Incidence of Stroke, Non CNS Systemic Embolism (SEE), Pulmonary Embolism (PE), Myocardial Infarction (MI), All Cause Death and Major Bleed [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]
  Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.
• Annualized Rate of Subjects With Minor Bleeds [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]

  Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

  Minor bleeds were clinical bleeds that did not fulfill the criteria for major bleeds. Minor bleeds were classified as associated with study medication discontinuation (temporary or permanent) or not.

• Annualized Rate of Subjects With Any Bleeds (Major Plus Minor) [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]
  Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.
• Annualized Rate of Subjects With Intra-Cranial Hemorrhage (ICH) [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]
  Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

The purposes of this study are:

1. To evaluate the long-term safety of dabigatran etexilate
2. To assess the effect of a knowledge translation intervention on patient outcomes

• Drug: dabigatran dose 1
  dabigatran high dose twice daily
• Drug: dabigatran dose 2
  dabigatran low dose twice daily

• Experimental: dabigatran dose 1
  dabigatran high dose twice daily
  Intervention: Drug: dabigatran dose 1
• Experimental: dabigatran dose 2
  dabigatran low dose twice daily
  Intervention: Drug: dabigatran dose 2

Inclusion criteria:

Participation in RE-LY, requires long term anticoagulation, provides written informed consent

Exclusion criteria:

Permanent discontinuation of dabigatran during RE-LY