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What is the Optimal Dosing for Unfractionated Heparin?
Abstract & Commentary
By Joseph E. Scherger, MD, MPH, Clinical Professor, University of California, San Diego. Dr. Scherger reports no financial relationship to this field of study.
Synopsis: Patients at high risk for VTE should be treated with three times daily UH, while patients at lower risk may be treated with twice daily therapy.
Source: King CS, et al. Twice vs three times daily heparin dosing for thromboembolism prophylaxis in the general medical population: a meta-analysis. Chest. 2007;131:507-516.
Clinical guidelines now recommend using prophylaxis against VTE in high risk hospitalized patients. Subcutaneous unfractionated heparin (UH) has become the treatment of choice due to its safety and ease of monitoring and administration. Patients who are commonly treated include any acutely ill patient confined to bed, such as one with heart failure, respiratory disease, and postoperative care. Patients with a previous history of DVT or PE are at particularly high risk and should be treated.
Dosage regimens of two times daily and three times daily are used and have never been compared according to these study authors, who did an extensive review of the literature from 1966 through 2004. Five thousand units subcutaneously is the usual dosage with both regimens. The authors from the Department of Medicine at Walter Reed Medical Center in Washington, D.C. performed the meta-analysis, looking at 447 articles over the 38 years. All but 12 of the articles were excluded, mainly because they studied surgical and postoperative patients. A total of 7978 patients were represented in these 12 studies, with 6314 receiving two times daily therapy and 1664 patients receiving three times daily therapy.
The patients receiving three times daily therapy had fewer episodes of VTE than those receiving twice daily therapy. Total VTE risk was not significantly different in the two groups (5.4 per 1000 patient days with twice daily compared with 3.5 in the three times daily patients, p = 0.87). The risk of PE was significantly lower in the three times daily group (0.5 per 1000 patient days compared with 1.5 in the twice daily group, p = .09). Also, the risk of proximal DVT and PE was significantly lower in the three times daily group (0.9 per 1000 patient days compared with 2.3 in the twice daily group, p = .05). This reduced VTE risk is offset some by a higher risk of bleeding complications in the three times daily group (0.96 per 1000 patient days compared with 0.35 in the twice daily group, p = .0001).
While a head-to-head study of these two dosage regimens is needed, this careful study indicated that three times daily dosing of UH is superior to twice daily dosing with some increased risk of bleeding complications. Note that the risk of bleeding in the three times daily group is lower than the risk of VTE, DVT or PE in the twice daily group.
So what should we do with this important study? A prudent recommendation would be to use three times daily therapy for all patients at high risk for VTE, such as patients with a past history of DVT or PE, and immobile patients in bed. In patients in which the risk of VTE is lower but prophylaxis is still warranted, twice daily therapy would be appropriate to reduce the risk of bleeding complications. We can all thank these authors for a painstaking analysis of 38 years of medical literature. I would hope that funding for a head-to-head study of these regiments is forthcoming since the differences here are small and a meta-analysis of studies in which none used both regimens is far from being definitive.