Do Patients Benefit From Dalteparin Bridging in the Postoperative Period?

Male surgeons working in operating room at hospital
The efficacy of postoperative bridging with dalteparin vs placebo was evaluated in those with AF or mechanical heart valves when warfarin is temporarily interrupted for a surgical procedure.

Postoperative dalteparin bridging did not prevent major thromboembolisms or bleeding events among patients with atrial fibrillation or mechanical heart valves. These findings from a prospective, double-blind, randomized controlled trial were published in The BMJ.

Patients (N=1471) with atrial fibrillation or mechanical heart valves who needed to interrupt warfarin due to a surgical procedure were recruited at 10 sites in Canada and India between 2007 and 2016 for the PERIOP2 trial. All patients stopped warfarin use 5 days prior to surgery and were given 200 IU/kg dalteparin 72 and48 hours before surgery and 100 IU/kg 24 hours before surgery. Patients were randomly assigned to receive daily dalteparin (n=821) or placebo (n=650) for at least 4 days following their procedure. Clinical outcomes through 90 days were assessed.

Patients had a mean age of 69.7 (SD, 12.3) years, 64.3% were men, 79.3% had atrial fibrillation only, 20.7% had mechanical valves, and 80.4% had hypertension.

Among the intervention cohort, patients with low risk for bleeding (n=287) received a mean dose of 15,256 IU and the patients at high risk (n=520) received a dose of 5024 IU dalteparin.

At 90 days, major thromboembolisms occurred among 1.0% of dalteparin and 1.2% of placebo recipients (risk difference, -0.3%; 95% CI, -1.3% to 0.8%; P =.64) and major bleeding events among 1.3% and 2.0% (risk difference, -0.7%; 95% CI, -2.0% to 0.7%; P =.32), respectively. Similar results were observed for the composite endpoint of major thromboembolism and bleeding events (risk difference, -0.9%; 95% CI, -2.6% to 0.8%; P =.28).

This study was limited by an error in randomization at 2 sites that caused all patients with atrial fibrillation who had low risk for bleeding to be assigned to the dalteparin intervention group. The imbalance was corrected at 2 other sites in which similar patients were randomly assigned in a 1:4 ratio to receive the dalteparin or placebo.

This study did not identify a benefit from dalteparin bridging among patients with atrial fibrillation or mechanical heart valves interrupting warfarin due to surgical intervention.

Disclosure: Pfizer supplied the study drug. Please see the original reference for a full list of disclosures.


Kovacs MJ, Wells PS, Anderson DR, et al; PERIOP2 Investigators. Postoperative low molecular weight heparin bridging treatment for patients at high risk of arterial thromboembolism (PERIOP2): double blind randomised controlled trial. BMJ. 2021;373:n1205. doi:10.1136/bmj.n1205