Venous thromboembolism prophylaxis with unfractionated heparin in the hospitalized medical patient: The case for thrice daily over twice daily dosing

For venous thromboembolism (VTE) prevention in the hospitalized medical patient, no head-to-head trials have been performed of unfractionated heparin (UFH) 5,000 U subcutaneously thrice (i.e. q8 h or TID) daily versus twice daily (q12 h or BID). Several meta-analyses have been undertaken in attempts to determine whether one regimen may be more beneficial for safety and efficacy. Currently, not all international guidelines include a recommended frequency for UFH. Delineation of this frequency may be helpful to the practicing clinician. Primary studies (with a modified Jadad score of ≥6 to demonstrate a stronger study design) that compared low molecular weight heparin (LMWH) and UFH, and UFH and placebo were evaluated. Meta-analyses evaluating safety and efficacy of LMWH versus UFH, or TID UFH versus BID UFH were also evaluated. Although BID UFH shows some efficacy in one primary study, it is no more beneficial than no prophylaxis in another study. LMWH appears to be more efficacious than BID UFH, but comparable in safety and efficacy to TID UFH. Meta-analytic data demonstrates that BID UFH may have some reduction in deep vein thrombosis. Meta-analytic data also suggests that TID UFH is more efficacious than BID UFH at the cost of more major bleeding. The medical patient with risk factors for the development of VTE appears to be at moderate to high risk. International guidelines for VTE prevention should incorporate a frequency for UFH to guide use. TID UFH is superior in efficacy to BID UFH even when taking into consideration the increased rate of major bleeds. Newly published risk-assessment models may be beneficial in determining which patients would best benefit from BID UFH or TID UFH.