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Associate Professor of Pharmacy School of Pharmacy Campbell University Buis Creek, North Carolina Clinical Assistant Professor of Medicine School of Medicine University of North Carolina Chapel Hill, North Carolina Clinical Pharmacy Specialist — Anticoagulation Moses Cone Health System Greensboro, North Carolina
Published Online, November 5, 2003. www.theannals.com, DOI 10.1345/aph.1C509b
The authors cited the "encouraged use" of low-dose UFH (LDUH), 5000 units subcutaneously 3 times-daily. Unfortunately, within the 67% (59/88) of accepted recommendations, they failed to differentiate between the percent acceptances of twice-daily versus 3-times-daily administration. Recognizing that "the LDUH regimen requires 1 or 2 additional subcutaneous injections daily compared with enoxaparin regimens" suggests the possibility that the treating physicians deferred recommendations for 3-times-daily in favor of twice-daily administration.
If the treating physicians who accepted recommendations for VTE prophylaxis conversion ordered UFH 5000 units 3 times daily, their decision still begs the question: Why was enoxaparin 30 mg administered twice daily in some patients, supposedly accounting for the "one additional subcutaneous injection daily," rather than 40 mg once daily? The MEDENOX (Prophylaxis in Medical Patients with Enoxaparin) study definitively demonstrated the effectiveness of enoxaparin 40 mg once daily in medical prophylaxis.2 If enoxaparin 30 mg twice daily was being used for thromboprophylaxis, it may have been more appropriate to channel cost reduction efforts toward ensuring the appropriate dosing of LMWH within their institution rather than attempt to substitute LDUH as VTE prophylaxis.
The authors reference several studies that demonstrated the equivalence of LMWH once daily to UFH 5000 units 3 times daily while citing a statistically significant reduction (56%) in the risk of anticoagulant-related major hemorrhage with LMWH. It should also be noted that several published randomized trials, which were powered to detect superiority, have demonstrated enoxaparin's superiority over LDUH.3,4
Further, Goldhaber et al.5 explored the role of UFH prophylaxis in patients at risk for VTE (Table 1). Fifty-six percent (n = 112) of patients who failed prophylaxis had been treated with pharmacologic modalities. In 61% of those cases, UFH had been administered as monotherapy and represented the highest prophylaxis failure rate compared with all other regimens. In 13 of 33 patients, pulmonary embolism factored as a major contributor to death, representing 39% of the study's overall 8.6% mortality rate.
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Regarding cost avoidance, a pharmacoeconomic model evaluating VTE prophylaxis based on MEDENOX criteria in 2 simulated cohorts of 3000 patients has estimated that enoxaparin accounted for 1.2–2.4% of the cost of an acute medical admission.6 The authors' projected medication cost avoidance appears inconsistent with the cost of the drug to a healthcare system versus average wholesale cost.
Finally, the authors' contention that healthcare facilities would reduce LMWH costs significantly if they adopted a pharmacy-driven, automatic substitution program among their nonsurgical candidates for VTE prophylaxis is of concern. A 33% rejection rate by treating physicians may well portend the acceptance of such a program within their own institution, but it should give pause to others contemplating similar methods. The American Medical Association does not support therapeutic substitution in what is essentially a therapeutic interchange of UFH for LMWH, 2 unique rather than identical medications. Further, the American Society of Internal Medicine is opposed to therapeutic interchange when an alternative drug is dispensed without the prescriber's authorization. Also, it is suggested that healthcare facilities may minimize liability risk by avoiding such financially driven decisions.
References
Related articles in The Annals:
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