A Bridge Over Troubled Water: When and When Not to Bridge Anticoagulation
A 56 year-old male previously on warfarin for treatment of DVT presented to the ED with flank pain. He had been unable to afford his medications for the past week, and thus had been off his warfarin. His INR was 1.3 on presentation, without any acute thrombosis-related complaints.
Do patients with brief interruptions in warfarin therapy require bridging to anticoagulation (AC) with heparin or heparin-analogues?
The vast majority of evidence related to indications for bridging to warfarin is in the perioperative setting. (1)
Traditionally, the decision of whether or not to bridge therapy for most patients on AC for AF depends on thromboembolic risk factors, best approximated by a CH2ADS2-VASc score > 2. (1)
CH2ADS2-VASc is a risk stratification system developed from large multi-center studies that included more than 1000 patients including the NICE trial and the Euro Heart Survey.
Incorporates CHF status, hypertension, age, diabetic history, and previous stroke status, among others to give risk stratification score for stroke.
Initial study and validation all conducted only on patients on anticoagulation for atrial fibrillation. (2)
The BRIDGE trial was a randomized, double-blind placebo controlled trial which enrolled 1884 patients with atrial fibrillation on anticoagulation that underwent elective invasive procedures, with and without bridging anticoagulation.
No significant reduction in thromboembolic events, with an increased relative risk of major bleeding, RR 2.43.
Major Bleeding is defined as drop in Hgb > 2 g/dL, requiring transfusion, or in an anatomically critical region.
Patients with mechanical heart valves, stroke, embolism, or TIA within 12 weeks of procedure were excluded from the trial. (3)
Risk of major bleeding increases with bridging to anticoagulation, with HAS-BLED score > 3 indicating significant bleeding risk independent of atrial fibrillation. (4)
HAS-BLED score developed from Euro Heart Survey on AF and includes hypertension, creatinine, stroke, bleeding history, INR, age, and drug history to assess for risk of major bleeding on anticoagulation for atrial fibrillation. (5)
A 2016 American Heart Association review analyzed a 34-study meta-analysis, the ORBIT-AF trial, the BRIDGE trial, and the Kaiser Permanente VTE study to recommend against bridging anticoagulation for most patients. (6)
Patients on AC for AF that were bridged experienced a 3x greater risk of major bleeding. (3)
Patients on AC for VTE that were greater than 1 year from time of initial thrombosis experienced no benefit with bridging. The Kaiser study did not include patients that were less than 1 year from time of VTE. (7)
For patients with prior VTE undergoing procedures, necessity for bridging depends on the time-frame of intervention.
A multicenter Lancet study that observed 712 patients on warfarin for VTE demonstrated that one month of therapy reduces risk of recurrent VTE to 10%, whereas three months of therapy reduced this risk to 5%. (8)
Thus, the American Heart Association recommends that patients that have been treated for less than 1 month for VTE should undergo bridging in the post-procedural setting.
The AHA recommends that patients with greater than 3 months of treatment for VTE do not need post-procedural bridging, but should receive standard DVT prophylaxis. (9)
Most studies on this topic are limited by the exclusion of non-AF patients and limitation to the perioperative setting.
In the absence of operation, risk of major bleeding is reasonably lower than with operative intervention.
Use of CH2ADS2-VASc to aid decision to bridge anticoagulation often results in non-clinically significant risk reduction and higher risk of major bleeding. (7)
For patients on anticoagulation for atrial fibrillation, this author recommends not bridging therapy after a pause in anticoagulation for any reason.
The ORBIT-AF and BRIDGE trials show no significant reduction in thromboembolic risk reduction and an increased risk of major bleeding. (7)
For patients on anticoagulation for VTE, this author recommends bridging if therapy has continued for less than 3 months, and no bridging if anticoagulated for greater than 3 months.
Lancet study demonstrates 10% risk of recurrent VTE within 1 month, and 5% risk after three months on warfarin. (8)
Kaiser Permanente study demonstrates no benefit of bridging for patients anticoagulated for greater than 1 year. (7)
Studies that examine volitional or non-operative pauses in anticoagulation are necessary.
Douketis, JD. Perioperative management of patients who are receiving warfarin therapy: an evidence-based and practical approach. Blood. 2011;117(9):5044-9.
Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk-factor based approach: the euro heart survey on atrial fibrillation. Chest. 2010 Feb; 137(2):263-72.
Douketiss JD, Spyropoulous AC, Kaatz S, Becker RC, Caprini JA, Dunn AS et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med. 2015;373(9):823-33.
Nishimura RA, Otto CM, Bonow RO, Carabellow BA, Erwin JP, Guyton RA et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014 Jun 10;63(22):2489.
Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010 Nov; 138(5):1093-100.
Rose AJ, Allen AL, Minichello T. A call to reduce the use of bridging anticoagulation. Circ Cardiovasc Qual Outcomes. 2016;9:64-7.
Clark NP, Witt DM, Davies Le, Saito EM, McCool KH, Douketis JD et al. Bleeding, recurrent venous thromboembolism, and mortality risks during warfarin interruption for invasive procedures. JAMA Internal Med. 2015;175:1163-68.
Research Committee of the British Thoracic Society. Optimum duration of anticoagulation for deep-vein thrombosis and pulmonary embolism. The Lancet. 1992; 340:873-6.
Kearon C, Hirsh J. Management of anticoagulation before and after elective surgery. N Engl J Med. 1997 May 22;336(21):1506-11.