Clinical question: in patients with atrial fibrillation, is peri-operative heparin bridging required during interruption of warfarin therapy?
Study design: randomized, double-blind placebo-controlled trial
Inclusion criteria:
- Age ≥ 18
- Permanent or paroxysmal atrial fibrillation / atrial flutter (confirmed by ECG / pacemaker interrogation), including valvular AF
- On warfarin for ≥ 3 months with a target INR of 2 – 3
- CHADS2 score ≥ 1 (congestive heart failure, hypertension, age > 75, diabetes, previous stroke)
- Undergoing invasive procedure / surgery requiring interruption of warfarin therapy
Exclusion criteria:
- Mechanical heart valve
- Stroke, TIA or systemic embolism within the last 12 weeks
- Major bleeding within the last 6 weeks
- Creatinine clearance < 30ml/min
- Platelet count < 100 x 109/L
- Planned for cardiac, intracranial or intraspinal surgery
- Heparin-induced thrombocytopaenia or heparin allergy
- Multiple planned procedures
Intervention:
- Patients randomized to bridging group or control group
- Bridging group: delteparin 100 IU/kg BD three days pre and 5-10 days post-procedure
- Control: subcutaneous placebo BD three days pre and 5-10 days post-procedure
Patient characteristics:
- 1884 patients, 934 in bridging group and 950 in placebo group
- Mean age 71.7 years
- Mean CHADS2 score of 2.3
- Approximately 40% on an antiplatelet, no difference in proportion of patients on antiplatelets
Outcomes and results:
- All outcomes assessed at 37 days post-procedure
- Primary outcomes at 30 days post-procedure:
- Arterial thromboembolism – 0.4% in bridging, 0.3% in placebo (p = 0.01 for non-inferiority, p = 0.73 for superiority)
- Major bleeding – 3.2% in bridging, 1.3% in placebo (p = 0.005 for superiority)
- Secondary outcomes
- Acute myocardial infarction – no difference
- Deep vein thrombosis – no difference
- Pulmonary embolism – no difference
- Minor bleeding – 20.9% in bridging, 12.0% in placebo (p < 0.001 for superiority)
Limitations:
- Use of CHADS2 vs CHADS2VASC2 score
- Male preponderance (73.4%)
- Mean CHADS2 score of 2.3, only 3% of patients with CHADS2 ≥ 5 (limited conclusions in high-risk patients)
- Numbers of actual thromboembolism were lower than expected – target power of the study had to be lowered, hence reducing chance that superiority of bridging over placebo could be detected
- Primary outcome of arterial thromboembolism assessed and defined by presence of clinical symptoms – smaller, sub-clinical events may have been missed
Conclusions:
- In patients on warfarin for atrial fibrillation, placebo was non-inferior to delteparin for the prevention of arterial thromboembolism
- Patients who are bridged peri-operatively with delteparin are at high risk of major bleeding
Reference: Douketis JD, Spyropoulos AC, Kaatz S, Becker RC, Caprini JA, Dunn AS, Garcia DA, et al. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation. N Engl J Med. 2015;373(9):823-33
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