BRIDGE - Peri-procedure bridging of anticoagulation of AF patients on warfarin
Bottom line: In patients with AF & CHADS2 score <4 requiring interruption of warfarin, bridging with parenteral anticoagulation increases major bleeding (NNH 53 from bridging) without reducing thromboembolic events.
Patients (n=1884)
Randomized 1884, analyzed 1813
Included
Atrial fibrillation or flutter (paroxysmal or permanent) confirmed by EKG or pacemaker interrogation
Non-valvular or valvular AF both eligible
CHADS2 score 1 or higher
Receiving warfarin for 3+ months with INR 2.0-3.0
Undergoing elective invasive procedure felt to require interruption of warfarin
Excluded
Mechanical heart valve
Recent stroke, systemic embolism or TIA (in past 12 weeks) or major bleeding (in past 6 weeks)
CrCl <30 mL/min
Platelets <100
Planned cardiac, brain or spine surgery
Baseline characteristics
Age 72 y, male (73%), white (91%)
CHADS2 score
Mean score 2.3
1 (23%), 2 (40%), 3 (24%), 4 (10%), 5 (3%), 6 (<1%)
HF/LV dysfunction ~33%
HTN 87%
Diabetes 41%
Prior stroke 8%
Prior TIA 8%
MI 15%
Undergoing procedure classified as having low bleeding risk 89%
Labs: INR 2.4, CrCl 88 mL/min
Concomitant ASA ~35%
Intervention & comparator
I: No bridging
Warfarin stopped 5 days before the procedure & restarted evening of surgery or POD 1, without bridging
C: Anticoagulant bridging
Warfarin stopped 5 days before the procedure & restarted POD0 evening or POD 1
Pre-op bridging: Dalteparin 100 units/kg subcut BID started 3 days before the procedure, last dose AM day before procedure (~24h before)
Post-op bridging: Dalteparin restarted 12-24h after low-bleeding-risk procedure & 48-72h after high-bleeding-risk procedure; continued x5-10 days until INR 2 or higher once
Adherence in both groups was ~86% pre-op & 96% post-op
Results @ day 30-37
Not bridging was non-inferior to bridging for the primary efficacy outcome (arterial thromboembolism; a composite of ischemic/hemorrhagic stroke, TIA, systemic embolism)
Intention-to-treat (ITT) population: No bridging 04.%, bridging 0.3% (difference 0.1%, 95% confidence interval [95%CI] -0.6% to +0.8%)
Stroke: 0.2% vs 0.3%
Per-protocol population: 0.3% vs 0.4% (difference 0.0%; 95% CI -0.7% to +0.7%)
Not bridging reduced the risk of major bleeding (ITT population): 1.3% vs 3.2% (NNT 53)
Minor bleeding: 12.0% vs 20.9% (NNT 12)
No difference in all-cause mortality: 0.5% vs 0.4%
Internal validity
Low risk of allocation, performance & detection bias
Interactive voice-response system
Dalteparin & matching placebo in identical vials
Blinded adjudication of all outcomes
Possible attrition bias due to moderate loss-to-follow-up (3.8%), which is higher than the rate of primary outcome events
Non-inferiority trial
Non-inferiority margin set as an absolute difference of 1.0% for arterial thromboembolism (wide);
Assumed ~1.0% absolute risk of arterial thromboembolism in both groups (actual event rate <1/2 expected);
Analysis of both ITT & per-protocol populations, which were nearly identical.