1) The document summarizes a study comparing the direct thrombin inhibitor dabigatran to warfarin for preventing thromboembolic events after cardioversion for atrial fibrillation. 2) The study found the risk of stroke and major bleeding within 30 days of cardioversion was low and comparable between the two doses of dabigatran tested and warfarin, with or without transesophageal echocardiography guidance. 3) The results suggest dabigatran is a reasonable alternative to warfarin for preventing thromboembolic events in patients requiring cardioversion for atrial fibrillation.

1. Michael G. Katz, MD
Cardiology Fellow, University of Rochester
Journal Club March 17, 2011

2.  I have not accepted any material gifts, favors,
or hospitality from any pharmacutical or
industry representatives in relation to this talk
 HOWEVER
 The prescription and maintenance of warfarin
(Coumadin®) prescriptions during Internal
Medicine residency has caused me a great
deal of frustration and emotional distress.

3.  US Adopted Name Council
 co-sponsored by the AMA, the United States
Pharmacopeial Convention (USP), and the American
Pharmacists Association (APhA).

4.  “duh-big-ga-tran” vs. “dabby-ga-tran”

6. Circulation 2011;123;131-136; originally published online Jan 3, 2011

7.  Cardioversion in atrial fibrillation is associated
with an increased thromboembolic risk.
 This is secondary to
 Pre-existing thrombi
 De novo thombus formation s/p cardioversion

9.  Without warfarin prior to DCCV: 1-7%
Am J Cardiol 1969;23:208–16
J Am Coll Cardiol 1992;19:851–5

10.  De novo:
 review of observational studies: rate TE after TEE
guided DCCV was 1.34% off anticoagulation
 Retrospective, observational study of 17 patients c
post-TEE guided DCCV off anticoagulation:
 None had thombus on initial TEE
 5 had echo smoke on initial TEE
 5 had post DCCV TEE
 4 had echo smoke
 1 had new thombus in LAA
Am Heart J. 1995;129(1):71-5
Circulation. 1994;89(6):2509-13.

11.  Almost all TE events in those who convert to
NSR occur within 10 days.
Am J Cardiol. 1998;82(12):1545-7, A8

12. Circulation 2006;114;700-752

13.  Per guidelines and given risk of post-DCCV TE,
there’s no way to escape the need to
anticoagulate for 4 weeks

14.  Not necessarily. ACUTE trial
 NEJM 2001;344:1411–20
 1222 pts screened with AF > 48 hours
 If initial TEE had thombus, 3 weeks of warfarin with
repeat TEE vs no TEE. All given 4 weeks post DCCV
anticoaguation.
 Both approaches were associated with comparably low
risks of stroke (0.81% with the TEE approach and 0.5%
with the conventional approach)
 The clinical benefit of the TEE-guided approach was
limited to saving time before DCCV

15. Total LOS:
6-8 hours

16. Circ Cardiovasc Qual Outcomes 2009; 2:297

17.  Narrow theraputic range
 Regular monitoring
 Interaction with foods and other medications
 Even in setting of randomized trials, patients
are only therapeutic approximately 2/3 of the
time.
 If you’re a resident, you may have to call
patients every time they eat a salad.

18.  direct reversible thrombin
inhibitor
 Oral pro-drug, dabigatran
etexilate, converted by serum
esterases to dabigatran
 bioavailability of 6.5%
 half-life of 12 to 17 h
 Peak plasma concentration
in 30 mins to 2 hours.
 Renally excreted by approximately
80%
 does not require regular dose
monitoring
 can be assessed by measuring
thrombin clotting time or ecarin
 clotting time, which might be
valuable in case of bleeding
J Am Coll Cardiol 2010;56:2067–76

20.  Dabigatran
 110 mg/150 mg
 b.i.d.
 Warfarin
 INR 2–3

21.  18,113 patients
 AF
 1 risk factor
 50% VKA naive
 CHADS2 0–1: 32%
 CHADS2 2:35%
 CHADS2 => 3: 33%

22.  Primary Endpoint:
 Composite: stroke/systemic embolism
 Secondary Endpoint:
 1. Myocardial infarction
 2. Pulmonary embolism
 3. Hospitalization
 4. Total mortality
 5. Cardiovascular mortality

23.  Event-driven (n=450), > 12 months

24.  Low-dose dabigatran non-inferior,
 High dose superior to warfarin

29. TEE encouraged if
cardioversion planned for
within 60 days of
randomization. TEE
guidance at discretion of
primary Cardiologist

30.  Major Outcomes
 Stroke and systemic embolism
 bleeding episodes

31.  Reduction in the hemoglobin level of at least
20 g/L
 Transfusion of at least 2 U blood
 Symptomatic bleeding in a critical area or
organ.

32.  Sudden onset of a focal neurological deficit in a
location consistent with the territory of a major
cerebral artery and
 Ischemic
 Hemorrhagic
 Unspecified

33.  therapy before (<3 or >=3 weeks), during, and after
cardioversion
 time in hours since the last dose of dabigatran
administered before cardioversion
 use of any nonstudy oral or systemic anticoagulant
and aspirin with or without clopidogrel.
 The method of cardioversion (electric or
pharmacological)
 TEE guided
 Spontaneous echo contrast or left atrial thrombi

34.  All cardioversions, and
 First cardioversion

36. D110 D150 warfarin
Adherence to ACC/AHA pre-cardioversion
guidelines was good and essentially similar.

37. D110 D150
Around ½ of study pts did not get drug <12 hours prior to DCCV.
The majority of those patients were not receiving heparin or non-
study anticoauglation

38. D110 D150 warfarin

40. While TEE was performed more frequently with dabigatran, there was
no significant difference in LA spontaneous echo contrast (21.2%,
27.2%, and 31.8% of TEEs in the D110, D150, and warfarin groups,
respectively) or LAA thrombus (1.8%, 1.2%, and 1.1%, respectively).

42.  Largest cardioversion experience to date
 The first to evaluate a novel anticoagulant
 Frequencies of stroke and major bleeding within 30
days of cardioversion on the 2 doses of dabigatran
were low and comparable to those on warfarin with or
without transesophageal echocardiography guidance
 Dabigatran is a reasonable alternative to warfarin in
patients requiring cardioversion