The RE-LY Study: Randomized Evaluation of Long-term anticoagulant therapY

1
The RE-LY StudyRandomized Evaluation of
Long-term anticoagulant therapY

• Dabigatran Compared to Warfarin in 18,113
  Patients with Atrial Fibrillation at Risk of
  Stroke

2
Atrial Fibrillation and Stroke

• AF responsible for 1/6 of all strokes
• Warfarin reduces stroke in AF by 64
• significant increase in intracranial and other
  hemorrhage
• Difficult to use
• Only 50 of eligible patients receive warfarin
• An alternative treatment is needed

3
Dabigatran

• Dabigatran Etexilate, a pro-drug, is rapidly
  converted to dabigatran
• 6.5 bioavailability, 80 excreted by kidney
• Half-life of 12-17 hours
• Phase 2 data identified 220 mg daily and 150 mg
  BID as viable doses

4
RE-LY A Non-inferiority Trial
Atrial fibrillation 1 Risk Factor Absence of
contra-indications 951 centers in 44 countries
PROBEProspective Randomized Open Trial with
Blinded Adjudication of Events.
R
open
Blinded
Dabigatran Etexilate 150 mg b.i.d. N6000
Warfarin (INR 2.0-3.0) N6000
Dabigatran Etexilate 110 mg b.i.d. N6000
10 efficacy outcome stroke or systemic
embolism 10 safety outcome major
bleeding Non-inferiority margin 1.46
5
Trial Execution

• Performed December 2005-March 2009
• Median Follow up 2.0 years
• Follow up 99.9 complete
• Mean TTR 64 (patients on warfarin)

6
Baseline Characteristics
7
Permanent Discontinuation
8
Stroke or Systemic Embolism
9
Primary Outcome
These, and all subsequent, p values, are for
superiority
10
Stroke Classification
11
Stroke or Systemic Embolism
12
All Intracranial Bleeding
13
Hemorrhagic Stroke
14
MI, Hospitalization and Death
15
Bleeding and Net Clinical Benefit
stroke, systemic embolism, myocardial
infarction, pulmonary embolism, death and major
bleed
16
Important Sites of Major Bleeding
17
Major Bleeding
18
Dabigatran 150 mg vs. 110 mg
19
ALT or AST gt3x ULN
20
Common Adverse Events
Occurred more commonly on dabigatran plt0.001
21
Conclusions

• Dabigatran 150 mg significantly reduced stoke
  compared to warfarin with similar risk of major
  bleeding
• Dabigatran 110 mg had a similar rate of stroke as
  warfarin with significantly reduced major
  bleeding
• Both doses markedly reduced intra-cranial and
  life-threatening hemorrhage
• Both doses are free of liver and other major
  toxicity, although they increase dyspepsia and GI
  bleeding

22
Conclusions

• Both Dabigatran doses offer advantages over
  warfarin
• Dabigatran 150 is more effective and dabigatran
  110 has a better safety profile
• The availability of two effective doses, with
  different benefit risk profiles, creates the
  potential to tailor therapy to individual patient
  characteristics