1. RE-ALIGN
Randomized, Phase II Study to Evaluate the Safety and Pharmacokinetics of Oral Dabigatran Etexilate in Patients after Heart Valve Replacement
Randomized, open-label
Two groups
undergoing implantation of a mechanical bileaflet valve in the aortic or mitral position or both (population A)
if they had undergone implantation of a mechanical bileaflet mitral valve (with or without mechanical bileaf let aortic-valve replacement) more than 3 months before randomization (population B)
Dosing regimens
150 mg twice daily in patients with a creatinine clearance of less than 70 ml per minute
220 mg twice daily in those with a creatinine clearance of 70 to 109 ml per minute,
300 mg twice daily in those with a clearance of 110 ml per minute or more
measured trough plasma levels of dabigatran
Study was discontinued early due to “excess thromboembolic and bleeding events among patients in the dabigatran group “

2. Results
Thromboembolic events occurred in the dabigatran group at all trough levels
“dabigatran is not appropriate as an alternative to warfarin for the prevention of thromboembolic complications in patients who require anticoagulation after the implantation of a prosthetic heart valve”
Possibly the mechanism of action of dabigatran limits its effectiveness for this type of thrombus formation
In vitro studies have demonstrated “high dose” rivaroxaban (300 ng/ml) is effective at preventing thrombus formation, while “low dose” rivaroxaban (30 ng/ml) was not

3. bleeding

4. The Concern
Warfarin has several reversal agents (Vitamin K, FFP, etc.)
Initially, there were no reversal agent for DOACs

5. Bleeding and Dabigatran: Data from RE-LY, RE-COVER, RE-COVER 2, RE-MEDY & RE-SONATE
Only 31% of major bleeds on warfarin received vitamin K, so the numbers probably should look even worse.
Significantly less Vitamin K and FFP used in the dabigatran group
PRBCs transfused more often in dabigatran group (possibly explained by the increased amount of GI bleeding in that group)

6. Intracranial Hemorrhage and Dabigatran
Data from RE-LY
Rates of intracranial hemorrhage are significantly lower at all sites with either dabigatran dose than warfarin
Data from the RE-LY trial

7. ICH Mortality and Dabigatran
Despite the absence of a specific reversal agent (at the time), there was no significant mortality increase in patients taking dabigatran

8. Predictors of ICH on Dabigatran
Age, prior CVA and ASA use were predictors of ICH with warfarin
Only age was a predictor of ICH in patients taking dabigatran