The risk of major bleeding in association with perioperative management of vitamin K antagonists is about 3% according to systematic reviews. We performed this study to evaluate the safety of perioperative management of dabigatran using a specified protocol.
Patients at least 18 years old, treated with dabigatran and planned for an invasive procedure were eligible for inclusion. The last dose of dabigatran before the procedure was at 24 h (creatinine clearance [CrCl] > 50 mL/min and standard bleeding risk), 48 h (CrCl 31-50 mL/h or increased bleeding risk) or 96 h (CrCl 31-50 mL/h and increased bleeding risk). Resumption was in the evening of the procedure with the first dose of 75 mg (hemostasis secured and low bleeding risk), postop day 1, 2 or 3, depending on the complexity of the surgery and consequences of a bleeding complication; all prespecified. Patients were followed for 30 days for major bleeding (primary outcome), minor bleeding, arterial thromboembolism and death and an independent committee adjudicated these events by. We calculated a sample size of 283 cases to exclude a doubling of major bleeding compared to historical warfarin with heparin bridging. The study was funded by Heart and Stroke Foundation Canada.
We included 286 patients, mean age of 70.6 years (standard deviation, 11.7), 44 (15%) patients had CrCl 31-50 mL/min and 2 (0.7%) had 30 mL/min or less. The planned procedure was considered as “increased bleeding risk” in 102 (36%) patients. The last dose of dabigatran was at 24, 48 and 96 h before surgery in 160, 103 and 23 patients, respectively. Resumption with 75 mg the same day was in 139 patients. Major bleeding occurred in 3 patients (1.05%; 2 adjudicated so far); a 70-year-old male underwent ultrasound-guided drainage of abdomen and was readmitted after 17 days due to rectal bleeding and light headedness; the second patient, an 81-year-old male bled more than expected during the procedure of wide resection of myxosarcoma with free flap rotation and received blood transfusions during surgery, and a 69-year-old male bled 1200 mL during hip revision arthroplasty and received 3 units of red cells. Minor bleeding was observed in 9 adjudicated cases and reported in 10 additional, so far not adjudicated, cases. There were no strokes, systemic emboli, transient ischemic attacks, venous thromboembolic events or deaths. Three serious adverse events were reported (chest pain, congestive heart failure, wound infection)
With our protocol for perioperative management of dabigatran the risk of major bleeding compares favorably with historical data on vitamin K antagonists.
Schulman: Bayer Healthcare: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Research Funding. Off Label Use: Dabigatran etexilate is an oral direct thrombin inhibitor approved for the prevention of stroke in patients with atrial fibrillation and (outside the US) for prevention of venous thromboembolism in patients undergoing total hip or knee replacement. This presentation includes discussion of the following off-label use of dabigatran: treatment of venous thromboembolism. Douketis:Boehringer Ingelheim: Consultancy, Honoraria. Lee:Boehringer Ingelheim: Honoraria. Heddle:CIHR: Research Funding; Canadian Blood Services: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Health Canada: Research Funding.