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Low molecular weight heparin (LMWH) for prophylaxis of deep venous thrombosis (DVT) can save money not because it’s inexpensive but because hospitalization, lab tests, and the use of intravenous equipment can be avoided.
Jan Haney, RN, care resource director for Group Health Northwest, an HMO in Spokane, WA, ran a study early last year to see how much her organization was saving when patients at risk for DVT are discharged early on enoxaparin (Lovenox) subcutaneously twice daily. She tracked two cases and concluded that they resulted in savings of $1,512 and $6,676 for the HMO. (See chart outlining expenses and savings, p. 131.) "Lovenox saves the plan an enormous amount of money mainly because it can be administered in the outpatient setting," says Haney.
Haney ran the study because physicians, as well as consultant groups, had requested information about the drug. One request came from a physician concerning a patient who needed some anticoagulation prior to a procedure. The patient was coming to a hospital in Spokane from a rural area.
"The provider," says Haney "wanted to know if it was feasible to start the therapy in a home setting in preparation for hospitalization. If that prepping can be done before admission, the patient doesn’t have to be brought into the hospital days ahead of the scheduled procedure, and lots of money is saved."
"Many nurses don’t realize that patients can be discharged with this drug," says Janice D. Nunnelee, MSN, RN, certified vascular clinical specialist at West County Family Practice in St. Louis. Administering LMWH outside the hospital clearly saves on hospital charges, but quality of care is improved as well because intravenous infusion of traditional unfractionated heparin limits mobility. In addition, patients welcome being at home for their treatments, and the risk of iatrogenic infection and its associated costs are avoided.
"Patients, particularly the DVTs who tend to remain in the hospital for extended periods, love not having to stay just for the purpose of getting their therapy," continues Haney. "And subcutaneous injections aren’t unusual in the outpatient setting. Family members and friends can be taught how to do them."
Lovenox was approved by the Food and Drug Administration (FDA) in 1993 for DVT prophylaxis before hip or knee surgery, and the agency’s Cardiovascular and Renal Drugs Advisory Committee has recommended that the drug receive approval for DVT treatment. It is also under consideration for unstable angina or non-Q-wave myocardial infarction.
DVT prophylaxis is administered subcutaneously twice daily for seven to 10 days. For treatment purposes, the drug is continued for a minimum of five days and until an INR goal of 2.0 to 3.0 is reached. Enoxaparin comes in 30- and 40-mg pre-filled syringes amounts smaller than most adults need. "Our pharmacy reformulates two or more doses into one," says Haney. The drug varies in cost based on geographic location and reformulation charges, but according to its manufacturer, Rhone-Poulenc Rorer, based in Collegeville, PA, a box of 10 30-mg syringes costs $168.10; a box of 10 40-mg syringes costs $224.02.
A number of trials over the past few years have studied the prophylactic use of enoxaparin in post-surgical patients at high risk for DVT. The drug has been found to be more effective than dextran, aspirin, and warfarin alone. The trials showed that LMWH significantly reduces the incidence of DVT without increasing bleeding complications when compared to low-dose standard heparin. The rate of DVT was so low in both groups, however, the clinical importance of this difference is questionable.
Patients undergoing hip surgery have a 40% to 80% incidence of DVT if no prophylaxis is administered. LMWH has been demonstrated to reduce the incidence of thrombosis by 50% compared to standard heparin. The risk of hemorrhagic complications was low and similar in both groups, although one large study showed a 42% to 45% reduction in both total and major bleeding complications among LMWH-treated patients.
Given the efficacy and safety demonstrated by LMWH in DVT prophylaxis, attention recently has shifted to use of LMWH for initial treatment of acute proximal DVT and pulmonary embolism. This use is not yet FDA-approved, but earlier this year, Rhone-Poulenc Rorer submitted a supplemental New Drug Application to the agency.
At least 19 clinical studies have compared unfractionated heparin to LMWH in this setting. The LMWH-treated groups received one of several LMWH preparations subcutaneously once or twice daily. The control groups received a bolus of standard unfractionated heparin, then dosing was adjusted to maintain therapeutic anticoagulation. Both groups began receiving oral warfarin between the second and tenth day, and that therapy was continued for at least three months. The LMWH or unfractionated heparin was discontinued after six to 10 days or when adequate anticoagulation was achieved. These studies, each enrolling between 40 and 432 subjects, uniformly found LMWH to be as effective and safe as standard heparin therapy.
No study found any advantages to unfractionated heparin, and no benefit in mortality was noted in either group. Many of the studies found trends in thromboembolic recurrence or bleeding favoring the use of LMWH, but the differences failed to reach statistical significance because of relatively small sample sizes.
A recent meta-analysis using data from nine studies found substantial advantages to LMWH over unfractionated heparin.1 The LMWH-treated patients had a 53% reduction in symptomatic recurrent thromboembolism and a 47% reduction in mortality compared to the standard heparin group. Venograms obtained before and after treatment showed significantly better improvement in the LMWH group. Major bleeding was reduced by 68% in the LMWH-treated group. All of these differences were statistically significant.
The most recent study of enoxaparin for cardiac therapy comes from Allegheny University Hospitals-Hahnemann Division in Philadelphia, where investigators demonstrated that LMWH’s therapeutic benefits outweigh its risks.2 The Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) trial concluded that antithrombotic therapy with enoxaparin plus aspirin is safe and effective in reducing ischemic events in patients with unstable angina and early non-Q-wave myocardial infarction (MI). Hemorrhage is the most common side effect associated with the use of heparins. There was no increased risk of major bleeding complications in the study.
ESSENCE looked at about 3,200 cardiac patients in 10 countries. Participants were randomized to either twice-daily 1 mg/kg subcutaneous enoxaparin and 100 to 325 mg aspirin once daily or adjusted-dose continuously infused unfractionated heparin and aspirin 100 to 325 mg once daily. They were treated within 24 hours of their last angina attack and given injections for a minimum of 48 hours and for as long as eight days.
Marc Cohen, MD, chairman of the ESSENCE trial, says patients medicated with Lovenox needed less costly treatment overall because they required fewer days in the hospital and ICU, and they required less blood level testing. Study participants in the enoxaparin group had significantly fewer revascularization procedures during the 30-day trial, and they had a significantly reduced incidence of angina. Two studies the year before came to similar conclusions. 3,4
Studies also show that LMWH significantly reduced DVT among patients with recent strokes without increasing bleeding complications compared to both placebo and standard heparin. Again, the incidence of DVT in this population is relatively low, and no consensus regarding the use of LMWH in this setting has been reached.
Studies have shown that LMWH is as effective as its unfractionated form at preventing clot extension and pulmonary emboli and is possibly safer. A number of unique properties make LMWH suitable for outpatient subcutaneous therapy for acute DVT. Compared to unfractionated heparin, LMWH has a much longer plasma half-life and excellent bioavailability after subcutaneous administration, allowing for once- or twice-daily dosing rather than continuous infusion.
"Because of its high degree of protein binding," says Nunnelee, "unfractionated heparin produces a variable anticoagulant effect, requiring daily monitoring of activated partial thromboplastin time and frequent dosage adjustment." LMWH, in contrast, produces a reliable anticoagulant effect in fixed dosages (adjusted for body weight) and does not require laboratory monitoring of its effect. Furthermore, early animal studies show that at equally therapeutic doses, LMWH induces hemorrhage less frequently than unfractionated heparin.
Five forms of LMWH are commercially available. Enoxaparin (Lovenox), manufactured by Rhône-Poulenc Rorer, is the first LMWH approved by the FDA for use in the United States. Preparations differ in their anticoagulant and pharmacokinetic properties, so results from studies of one drug may not generalize to other preparations.