The BRIDGE Trial and NOACS: A Quiz

The BRIDGE trial was a randomized controlled trial in patients with atrial fibrillation (AF) of bridging anticoagulation during interruption of warfarin for elective invasive procedures. Subjects’ mean CHA₂DS₂-Vasc score was 2.6 (range 1 to 4). 

Q1. What was the rate of arterial thromboembolism at 30 days in the no-bridging group?

A. 0.4%

B. 1.4%

C. 2.4%

D. 3.4%

E. 4.4%

Answer, discussion, and question 2, next page.

Answer: A. 0.4%

The rate of arterial thromboembolism was 0.4% at 30 days in the non-bridging group and 0.3% in the group that received bridging therapy.¹

Despite the absence of anticoagulation and given the possibility of a more prothrombotic state in the periprocedural period, the rate of arterial events was quite low at 30 days. This suggests that the risk of thromboembolism in the periprocedural setting, even in patients with a relatively high mean CHA₂DS₂-Vasc score, may have been overestimated in the past. Obviously, the risk of arterial thromboembolism is also linked to the type of procedure and to fluctuations in blood pressure.¹

Q2. In the BRIDGE trial, what was the approximate risk of periprocedural major bleeding with LMWH bridging vs. non-bridging?

A. ~1X

B. ~2X

C. ~3X

D. ~4X

E. ~5X

Answer, discussion, and question 3, next page.

Answer: C. ~3X. 

Major bleeding occurred in 1.3% of patients in the non-bridging group and in 3.2% in the bridging group (RR 0.41; 95% CI 0.20-0.78, p=0.005). Minor bleeding was also higher in the bridging group (20.9% vs 12.0%, P<.001). Since there was no difference in the efficacy outcomes (arterial thromboembolism, acute MI, DVT, PE, death) and better bleeding event rates, the authors concluded that forgoing bridging anticoagulation was noninferior to bridging with a lower risk of major bleeding.¹

Q3. Which of the following patients with AF should probably receive bridging therapy prior to an invasive procedure?

A. 88-year-old female with a bioprosthetic aortic valve.

B. 49-year-old male with a history of a bicuspid aortic valve s/p mechanical valve replacement.

C. 79-year-old male with a history of CABG, LVpEF, and left atrial appendage ligation.

D. 62-year-old female who had atrial flutter and is s/p atrial flutter ablation without recurrence.

Answer, discussion, and question 4, next page.

Answer: B. A 49-year-old male with a history of a bicuspid aortic valve s/p mechanical valve replacement.

The ACC/AHA atrial fibrillation guidelines recommend bridging therapy with unfractionated or low molecular weight heparin for all patients with mechanical heart valves who require periprocedural interruption of warfarin. (Class I, Level of Evidence C).²

Q4. If a patient is taking one of the novel oral anticoagulants (NOACs) and requires periprocedural bridging, how long after the last dose of NOAC should parenteral anticoagulation be initiated for NOACs that are dosed BID?

A. 6 hours

B. 12 hours

C. 18 hours

D. 24 hours

E. 48 hours

Answer, discussion, and question 5, next page.

Answer: B. 12 hours

For most NOACs, parenteral anticoagulation should be started ~12 hours after the last dose. The exception is rivaroxaban as it is dosed once daily so there should be a full 24h between last oral dose and initiation of parenteral therapy. Following are specific recommendations:        

Apixaban: Wait 12 hours after last dose to initiate parenteral anticoagulant.

Dabigatran: If CrCl >30 mL/min, wait 12 hours after last dose to initiate parenteral anticoagulant. If CrCl <30 mL/min, wait 24 hours after last dose to initiate parenteral anticoagulant.

Rivaroxaban (15 mg, 20 mg): Wait 24 hours after rivaroxaban discontinuation to initiate parenteral anticoagulant.

Rivaroxaban (10 mg): Initiate parenteral anticoagulant as clinically needed irrespective of time of last rivaroxaban dose.

Q5. For which of the NOACs is a parenteral bridge usually recommended when transitioning to warfarin?

A. Apixaban

B. Dabigatran

C. Rivaroxaban

D. A and C

E. None of the above

Answer and discussion, next page.

Answer: D.  A. Apixaban and C. Rivaroxaban

Results of the ROCKET-AF trial raised concerns about the potential for rebound hyercoagulability in the setting of discontinuation of the factor Xa inhibitors. Therefore, it is recommended to consider (although not absolutely indicated) bridging anticoagulation with parenteral agents when transitioning patients from apixaban or rivaroxaban to warfarin until the INR is between 2-3.³

References    

1. Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative bridging anticoagulation in patietns with atrial fibrillation. N Engl J Med. 2015;373:823-33. doi: 10.1056/NEJMoa1501035. Epub 2015 Jun 22.         

2. January CT, Wann L, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64:2246-2280. doi:10.1016/j.jacc.2014.03.021.

3. Reynolds MR. Discontinuation of rivaroxaban: filling in the gaps. J Am Coll Cardiol. 2013;61:659-660. doi:10.1016/j.jacc.2012.09.056.