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Dabigatran
NAGESH JADAV
Anticoagulation
Standard therapeutic approach to many cardiovascular
disease.
As an example, in patients with atrial fibrillation (AF),
anticoagulation is known to reduce the reported 2% to
18% annual risk of embolic stroke for patients with a
CHADS score of 1 to 6 by two-thirds [
Until recently, warfarin has been the only available oral
anticoagulant exhibiting a positive benefit-risk profile
when the extent of anticoagulation is carefully
monitored and managed with dose adjustments.
The global introduction of several novel oral
anticoagulants (NOACs) has recently transformed the
clinical practice of oral anticoagulation.
ANTICOAGULANTS
Dabigatran
Orally given Direct Thrombin Inhibitor
Approved for
Preventions of stroke for patients with Non valvular AF- 2012
VTE/PE
VTE prophylaxis post orthopedic surgeries- 2008
Eliminated renally
Less and less drug interaction than the conventional rat poison
*Use of PCC
Thromb Res. 2015;135:544-7.
*Use of hemofiltration
Clin J Am Soc Nephrol. 2013;8:1533-9.
Dabigatran and Bleeding
Major Bleeding
Moderate Bleeding
•discontinue treatment compression a) Prothrombinex-VF
as appropriate. •Surgical intervention 25-50 IU/kg b)
•Apply local measures or wound packing FEIBA 50 IU/kg
and treat any •Administer fluid c) Tranexamic acid
aggravating factors replacement to 15-30 mg/kg IV+/-
maintain good urine infusion for mucosal
output as dabigatran bleeds
is renally excreted. •Consider dialysis for
•Consider platelets if dabigatran,
levels less than 70-80 •Neither pro-
x 109/L or patient on haemostatic agents or
anti-platelet agent. dialysis improve
•Oral activated outcome in pts taking
charcoal if ingested in dabigatran with a
last two hours. normal APTT or level
of < 50 ng/mL.
•Consult Haemotology
Phase 1 trails:
Glund S, Stangier J, Schmohl M, et al. Safety, tolerability, and
efficacy of idarucizumab for the reversal of the anticoagulant
effect of dabigatran in healthy male volunteers: a randomised,
placebo-controlled, double-blind phase 1 trial. Lancet.
Group B
• Requiring Surgery or invasive
procedure
Study Treatment
Patient received 5gm of study drug IV,
administered as 2 x 50ml boluses over 5-10mins
infusion 10mins apart
Analysis
Blood samples were obtained at baseline, after
the first infusion of idarucizumab, and then
between 10 and 30 minutes and at 1, 2, 4, 12,
and 24 hours after the second infusion
Secondary End-Point
• Proportion of patient who had complete
normalization of dilute thrombin time or escarin time
in first 4hrs and the reduction of dabigatran level
• Clinical Outcome: Extent of bleeding, hemodynamic
instability, Severity of bleeding, ICH patient, Death
defined as vascular or non vascular
Baseline
18 death overall with 9 in each group
5 fatal bleeding
2 septic shock
3 intracranial bleeding
21 Adverse event
Analysis
BOX &
WHISKER
PLOTS
Ok
Cost is 3800
Strength of the study
Broad inclusion criteria
Of the 90 patients, 64% had taken their last dose of dabigatran more than
12 hours prior to idarucizumab infusion. Of these, 30% had taken it greater
than 24 hours prior. Since the half-life of dabigatran is 12 to 17 hours, this
raises the question of whether patients were truly anticoagulated at the time
of idarucizumab infusion.
This is only an interim analysis and will have to wait for complete report
Thanks