Heparin versus enoxaparin for prevention of venous thromboembolism after trauma: A randomized noninferiority trial.

BACKGROUND

Research comparing enoxaparin with unfractionated heparin (UFH) given every 12 hours for venous thromboembolism (VTE) prophylaxis after trauma overlooks original recommendations that UFH be given every 8 hours. We conducted a prospective, randomized, noninferiority trial comparing UFH every 8 hours and standard enoxaparin every 12 hours. We hypothesized that the incidence of VTE in trauma patients receiving UFH every 8 hours would be no more than 10% higher than that in patients receiving enoxaparin every 12 hours.

METHODS

Trauma patients who met criteria for VTE prophylaxis at a Level I trauma center were randomly assigned to 5,000-U UFH every 8 hours or 30-mg enoxaparin every 12 hours between November 2012 and September 2014. Surveillance duplex ultrasound was performed twice weekly on intensive care unit patients and weekly on ward patients. Primary end points were deep vein thrombosis diagnosed by duplex ultrasound and pulmonary embolism diagnosed by computed tomography angiography.

RESULTS

Of 495 randomized patients, 220 received UFH and 216 received enoxaparin for analysis. Overall, 105 in the UFH group and 103 in the enoxaparin group underwent VTE surveillance or diagnostic testing. In the analysis of randomized patients who received treatment, UFH was noninferior compared with enoxaparin (absolute VTE risk difference, 3.1%; 95% confidence interval, -1.6% to 7.7%; p = 0.196); however, in the screening ultrasound group, the noninferiority of UFH was inconclusive (absolute VTE risk difference, 6.5%; 95% confidence interval, -2.9% to 15.8%; p = 0.179). The two treatments did not differ with regard to adverse events. The pharmaceutical cost for the regimen of UFH ($2,809) was nearly 20-fold lower than that for enoxaparin ($54,138).

CONCLUSION

A regimen of UFH every 8 hours may be noninferior to enoxaparin every 12 hours for the prevention of VTE following trauma. Given UFH's cost advantage, the use of UFH for VTE prophylaxis may offer greater value.

LEVEL OF EVIDENCE

Therapeutic/care management study, level II.