Current issues of ACP Journal Club are published in Annals of Internal Medicine


Enoxaparin increased costs but reduced thromboembolic risk compared with low-dose warfarin after hip replacement surgery

ACP J Club. 1995 Nov-Dec;123:83. doi:10.7326/ACPJC-1995-123-3-083

Source Citation

Menzin J, Colditz GA, Regan MM, Richner RE, Oster G. Cost-effectiveness of enoxaparin vs low-dose warfarin in the prevention of deep-vein thrombosis after total hip replacement surgery. Arch Intern Med. 1995 Apr 10;155:757-64.



To compare the cost-effectiveness of enoxaparin sodium with low-dose warfarin sodium in preventing deep venous thrombosis (DVT) after total hip replacement surgery.


A decision-analytic model comparing the 2 treatment strategies with no prophylaxis in a hypothetical cohort having total hip replacement surgery. The expected number of patients to develop DVT or pulmonary embolism (PE), the expected number of thromboembolic deaths, and the expected costs of venous thromboembolic care were estimated from the published literature.


North America.


A hypothetical cohort of 10 000 patients having elective total hip replacement surgery.


Patients were assigned to placebo, low-dose warfarin (adjusted to maintain the international normalized ratio between 2 and 3), or subcutaneous enoxaparin sodium, 30 mg twice daily. Treatment was started ≤ 24 hours after surgery and was maintained ≥ 7 days.

Main cost and outcome measures

Number of cases of confirmed DVT and PE, number of thromboembolic deaths, and the cost-effectiveness ratios of low-dose warfarin compared with no prophylaxis and enoxaparin compared with low-dose warfarin.

Main results

Among 10 000 patients who received no prophylaxis, an estimated 979 patients developed confirmed DVT, 217 developed confirmed PE, and 259 died of thromboembolism. Low-dose warfarin would be expected to reduce the number of patients with confirmed DVT to 417, those with confirmed PE to 92, and those dying of thromboembolism to 110. Warfarin would also reduce the expected costs of care related to DVT from U.S. $530 to $330 per patient. Enoxaparin would further reduce the number of patients with confirmed DVT to 252, confirmed PE to 56, and thromboembolic deaths to 67, but at a cost of $383 per patient. The incremental cost-effectiveness ratio of enoxaparin, relative to low-dose warfarin, is estimated to be approximately $12 300 per death averted.


Use of enoxaparin after total hip replacement surgery increased patient-care costs compared with prophylaxis with low-dose warfarin but reduced the risk for thromboembolism.

Source of funding: Rhône-Poulenc Rorer Pharmaceuticals Inc.

For article reprint: Dr. G. Oster, Policy Analysis Incorporated, 4 Davis Court, Brookline, MA 02146, USA. FAX 617-232-1155.


Low-molecular-weight heparins act as antithrombotic agents by inhibiting the activity of factor Xa. They have a longer half-life than standard heparin and can be given in a subcutaneous fixed dose without daily laboratory monitoring of anticoagulation status. For these reasons, they have great potential as agents for preventing thrombosis.

The study by Menzin and colleagues confirms previous findings that low-dose warfarin, compared with no prophylaxis, saves costs by preventing DVT after total hip replacement (1, 2). This study also shows that enoxaparin is more effective than low-dose warfarin, with estimated DVT incidence rates of 13.6% and 22.5%, respectively. On the basis of these estimates, the cost-effectiveness of enoxaparin should be interpreted with some caution because no published randomized trial has directly compared enoxaparin with low-dose warfarin for DVT prophylaxis after surgery. To estimate the relative effectiveness of the 2 drugs, the authors used pooled data from trials of each. In these cases, examining the sensitivity analyses is especially important: If the assumed incidence of DVT with enoxaparin is varied from 10.9% to 16.3%, the cost per additional death averted varies from approximately $4900 to $26 100. These estimates are similar to those of a recent study by O'Brien and colleagues (3) and compare favorably with other medical interventions. Of note, both studies were funded by the manufacturer of enoxaparin.

Although thrombosis prophylaxis is clearly both effective and cost-effective after total hip replacement, the rate of prophylaxis remains low (4) despite consensus recommendations. A prevailing concern is the risk for bleeding after surgery. For the same antithrombotic activity, enoxaparin may cause less hemorrhage than unfractionated heparin because it does not inhibit platelet aggregation or impair vascular permeability to the same degree. The comparative risks for bleeding of enoxaparin and low-dose warfarin in DVT prophylaxis after surgery, however, remain to be determined. If the risk for serious bleeding is higher with enoxaparin than with warfarin, enoxaparin will be less cost-effective and less attractive.

Angela M. Cheung, MD
New England Deaconess HospitalBoston, Massachusetts, USA


1. Oster G, Tuden RL, Colditz GA. A cost-effectiveness analysis of prophylaxis against deep-vein thrombosis in major orthopedic surgery.JAMA. 1987;257:203-8.

2. Paiement GD, Wessinger SJ, Harris WH. Cost-effectiveness of prophylaxis in total hip replacement. Am J Surg. 1991;161:519-24.

3. O'Brien BJ, Anderson DR, Goeree R. Cost-effectiveness of enoxaparin versus warfarin prophylaxis against deep-vein thrombosis after total hip replacement. CMAJ. 1994:150:1083-90.

4. Anderson FA Jr, Wheeler HB, Goldberg RI, et al. Physician practices in the prevention of venous thromboembolism. Ann Intern Med. 1991;115:591-5.

Commentary update

Randomized controlled trials have now compared warfarin with low-molecular-weight heparin (LMWH) (1). LMWH has become almost standard practice in many settings (e.g., treatment of venous thrombolism [VTE] and prophylaxis against VTE events after hip surgery). Costs may vary in different settings, and this review may therefore be less relevant.

1. Hull RD, Pineo GF, Francis C, et al. Low-molecular-weight heparin prophylaxis using dalteparin extended out-of-hospital vs in-hospital warfarin/out-of-hospital placebo in hip arthroplasty patients: a double-blind, randomized comparison. North American Fragmin Trial Investigators. Arch Intern Med. 2000;160:2208-15.