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Assistant Director of Pharmacy Brigham and Women's Hospital Boston, Massachusetts 02115 FAX 617/566-2396 jfanikos{at}partners.org
Assistant Director, Anticoagulation Clinic Brigham and Women's Hospital
Published Online, November 5, 2003. www.theannals.com, DOI 10.1345/aph.1C509a
LMWH utilization has increased because, as a class, these drugs represent an improvement over UFH. With enhanced bioavailability, longer half-life, preferential factor Xa inhibition, and reduced adverse effects, LMWHs provide a more predictable level of anticoagulation.2 In the setting of acute thrombosis, recent studies have shown the difficulties associated with UFH administration, laboratory monitoring, and dosing changes required to maintain therapeutic anticoagulation.3,4 In fact, Hylek recommends the substitution of LMWHs for UFH.
Superiority of LMWHs in the surgical setting is reflected in the American College of Chest Physicians Sixth Consensus Conference on Antithrombotic Therapy. LMWHs are the recommended agents in hip/knee replacement, trauma, and spinal cord injury.5
In the setting of nonsurgical patients, the superiority of LMWH prophylaxis is not as clear. The clinical trials are limited in number and patient enrollment is small. Furthermore, there are no trials comparing UFH every 8 hours and every 12 hours. The authors cite PRINCE (Thromboembolism Prevention in Cardiopulmonary Diseases with Enoxaparin), a trial that was designed for and showed LMWH and UFH equivalence. What was disconcerting in that trial was the significantly higher rates of adverse drug events in the UFH group (53.8% vs. 45.8%). Elevations in aminotransferases were more frequent in UFH-treated patients than in LMWH-treated patients (12.6% vs. 7.2%). Injection site hematoma was more common with UFH (12.6% vs. 7.2%). The PRIME (Thromboembolism Prophylaxis in Internal Medicine with Enoxaparin) study also showed efficacy equivalence, but with a similar sacrifice in liver enzyme elevations and increases in injection site hematoma. Clearly, hematomas are not life threatening, but are a worrisome event to the patient and the provider.
Carroll and Hudson provided provocative data on pharmacy cost savings; however, additional information would be helpful for us to consider this strategy. There is little information on baseline characteristics, efficacy, and safety results. Specific criteria were not stated for bleeding or adverse events, although the authors did monitor patients throughout their stay. They searched for patients receiving enoxaparin twice daily. How many patients were identified, and would converting to a once-daily regimen have saved money? Were all patients converted to a UFH 3-times daily regimen, or was a twice-daily regimen allowed as well? Did any physicians simply opt to discontinue all prophylaxis regimens? Because nursing workload increases when moving from a once- to a 3-times-daily dosing regimen, nurses will frequently contribute to therapeutic decisions. Was prophylaxis duration identical between groups? Were any adverse events seen in the PRINCE and PRIME trials identified? Heparin-induced thrombocytopenia is a complication of UFH even with prophylactic doses.
Several authors have pointed to how poorly prophylaxis is prescribed in the hospital.6 Do pharmacists reinforce that behavior by turning to an older, more frequently administered agent with troublesome adverse effects? Pharmacists' time may be better utilized in identifying medical patients at risk for venous thromboembolism with no preventive strategy and offering an intervention.
Footnotes
Comments on articles previously published are submitted to the authors of those articles. When no reply is published, either the author chose not to respond or did not do so in a timely fashion. Comments and replies are not peer reviewed.–ED.
References
Related articles in The Annals:
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