Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation

Jatin Patel, PharmD Candidate 2016, Mercer University College of Pharmacy

Per the package insert, Coumadin® (warfarin) is indicated for prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation and reduction in the risk of thromboembolic events such as stroke or systemic embolization after myocardial infarction. In addition, the package insert states Coumadin® can cause major or fatal bleeding, therefore regular monitoring of international normalized ratio (INR) needs to be performed in all treated patients. The package insert also recommends, patients with non-valvular atrial fibrillation taking warfarin, the targeted INR should be 2.5.1

According to the Journal of Circulation, bridging anticoagulation refers to giving a short-acting blood thinner, like low-molecular-weight heparin, for 10 to 12 days around the time of surgery/procedure when warfarin is stopped, usually for 5 to 6 days before surgery. The article also states that bridging is started 3 days before surgery until last dose is given 24 hours before surgery and is resumed no earlier than 24 hours after surgery. In addition, warfarin is restarted after surgery and bridging is continued, generally for 4 to 6 days until targeted INR is reached.2

Title: Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation
Design Randomized, double-blind, placebo-controlled trial
Objective To determine in patients with atrial fibrillation, if forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding
Study Groups Forgoing bridging anticoagulation (no-bridging/placebo) and bridging anticoagulation therapy with low-molecular-weight heparin
Methods Patients were randomly assigned to receive bridging anticoagulation therapy with Fragmin® (dalteparin sodium) (100 IU per kilogram of body weight administered subcutaneously twice daily) or to receive no-bridging therapy from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. Warfarin was stopped 5 days before the procedure and was restarted on the evening of or the day after the procedure. Dalteparin or placebo administration was resumed 12 to 24 hours after a low-bleeding-risk procedure and 48 to 72 hours after a high-bleeding risk procedure. Patient continued to take study drug until INR was 2 or higher on one occasion.
Duration July 2009 through December 2014
Primary Outcome Measure The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding.
Baseline Characteristics
No-Bridging (N=950) Bridging (N=934)
Age 71.8±8.74 71.6±8.88
Race – White 90.5% 90.9%
Hypertension 87.7% 86.3%
Stroke 8.3% 10.6%
Transient ischemic attack 8.3% 8.2%
INR 2.4±0.57 2.4±0.57
Results The study recruited 1884 patients in which 950 patients were assigned to the placebo group and 934 patients were assigned to the bridging group. The incidence of arterial thromboembolism was 0.4% in the no-bridging group and 0.3% in the bridging group at 30 days after the procedure (risk difference, 0.1 percentage points; 95% confidence interval [CI], −0.6 to 0.8; p = 0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; p = 0.005 for superiority).
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: minor bleeding (16.4%), major bleeding (2.3%), myocardial infarction (1.2%), stroke (0.3%), transient ischemic attack (0.1%), deep-vein thrombosis (0.1%), pulmonary embolism (0.1%), and death (0.5%)
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreased the risk of major bleeding.

The study states that forgoing bridging anticoagulation was noninferior to the use of bridging anticoagulation for the prevention of arterial thromboembolism. The overall rate of arterial thromboembolism was lower than expected which potentially affected the power of the trial to detect a benefit associated with bridging. Furthermore, the observed rate of major bleeding in the bridging group may be considered to be modest due to protocol was designed to minimize bleeding. The trial findings may also apply to the newer direct oral anticoagulants if the trial findings have diminished relevance because of the decreasing use of warfarin in the treatment of patients with atrial fibrillation.3

Reference:

  1. Coumadin® [package insert]. Princeton, NJ: Bristol-Myer Squibb; Revised October 2011.
  2. Bridging Anticoagulation: Is it Needed When Warfarin is Interrupted Around the Time of a Surgery or Procedure?. Circulation. 2012;125(12):e496-8.
  3. Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation. N Engl J Med. 2015.
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