In medical patients, it is unclear whether thromboprophylaxis with low dose unfractionated heparin (UFH) should be administered twice (bid) or thrice daily (tid).

METHODS: Mixed-treatment comparison meta-analysis of randomized control trials that enrolled hospitalized nonsurgical patients at risk of venous thromboembolism and compared UFH bid, UFH tid, or low molecular weight heparin (LMWH) to each other or to an inactive control and measured deep venous thrombosis (DVT), pulmonary embolism (PE), major bleeding and/or death. A Bayesian framework using a random-effects model was applied.

RESULTS: 16 trials with moderate methodologic quality that enrolled 27,667 patients contributed to this analysis. The relative risk and 95% credible intervals comparing UFH tid to UFH bid for DVT, PE, death and major bleeding were 1.56 (0.64 to 4.33), 1.67 (0.49 to 208.09), 1.17 (0.72 to 1.95) and 0.89 (0.08 to 7.05); respectively. When compared to either dose of UFH, the use of LMWH has an effect similar to UFH on all four outcomes.

CONCLUSIONS: Moderate quality evidence suggests that subcutaneous UFH twice daily and UFH thrice daily do not differ in effect on DVT, PE, major bleeding and mortality. Either of the two dosing regimens of UFH or LMWH appears to be a reasonable strategy for thromboprophylaxis in medical patients. A future randomized trial comparing the two doses of UFH is very unlikely, considering the very large sample size that would be required to demonstrate a significant difference, which, if it exists, is undoubtedly small.