Enoxaparin prevented more DVT than did warfarin after knee arthroplasty
ACP J Club. 1996 July-Aug;125:4. doi:10.7326/ACPJC-1996-125-1-004
Leclerc JR, Geerts WH, Desjardins L, et al. Prevention of venous thromboembolism after knee arthroplasty. A randomized, double-blind trial comparing enoxaparin with warfarin. Ann Intern Med. 1996 Apr 1;124:619-26. [PubMed ID: 8607589]
To compare the efficacy and safety of fixed-dose enoxaparin and adjusted-dose warfarin to prevent deep venous thrombosis (DVT) after knee arthroplasty.
Randomized, double-blind, placebo-controlled trial with 6-month follow-up.
8 university hospitals in Canada.
670 adults (mean age 69 y, 63% women) who had knee arthroplasty. Exclusion criteria were allergy to study medications or contrast material, need for anticoagulant or antiplatelet agents, bleeding diathesis, gastrointestinal hemorrhage, renal or hepatic insufficiency, substance abuse, or recent hemorrhagic stroke. Follow-up was complete.
After surgery, 334 patients were assigned to warfarin to maintain the international normalized ratio between 2.0 and 3.0, plus subcutaneous saline placebo. 336 patients were assigned to enoxaparin, 30 mg subcutaneously every 12 hours, plus warfarin placebo once daily. Warfarin was started on the evening of surgery, and enoxaparin was started the following morning. Medications were given for 2 weeks or until hospital discharge, whichever came first. No other thromboprophylactic agents or antiembolic stockings were used.
Main outcome measures
Incidence of DVT in patients with adequate bilateral venograms, pulmonary embolism, death, and adverse events. Secondary end points were the need for transfusion and major, minor, and total bleeding.
62% of patients had venograms adequate to assess DVT. Patients receiving enoxaparin compared with those receiving warfarin had a decreased incidence of DVT (51.7% vs 36.9%, P = 0.003) (Table). More patients in the enoxaparin group needed transfusions (42.0% vs 32.3%, P = 0.01). The groups did not differ for mortality (1 death in each group); proximal thrombosis (11.7% vs 10.4%, P > 0.2); bleeding; pulmonary embolism; or other adverse events.
Fixed-dose enoxaparin was more effective than adjusted-dose warfarin in reducing deep venous thrombosis in adults who had knee arthroplasty. The incidence of death, pulmonary embolism, proximal thrombosis, and bleeding were similar in each group.
Source of funding: Rhône-Poulenc Rorer, Canada.
For article reprint: Dr. J.R. Leclerc, Cardiovascular Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA. FAX 317-277-3148.
Table. Enoxaparin vs warfarin after knee arthroplasty*
|Outcome at 6 mo||Enoxaparin||Warfarin||RRR (95% CI)||NNT (CI)|
|Incidence of DVT||37%||52%||29% (11 to 43)||7 (4 to 19)|
*Abbreviations defined in Glossary. RRR, NNT, and CI calculated from data in article.
DVT is a major and frequent complication of knee arthroplasty. Low-molecular-weight heparin (LMWH) has emerged as a safe and effective approach to DVT prevention, and this study adds important data on the comparison between LMWH and warfarin.
As compared with patients in the LMWH arms of some previous studies (1), the patients receiving LMWH in the Leclerc study had a lower incidence of major bleeding and a higher incidence of proximal DVT, possibly related to the later start of enoxaparin after surgery. Starting enoxaparin later after knee arthroplasty may be safer, but its advantage over warfarin in preventing proximal DVT may be lost. These observations, however, are based on between-study differences and should be subjected to further testing.
In this trial, warfarin was started on the evening of surgery, and enoxaparin, the morning after surgery. Although the anticoagulant effect of warfarin begins within 24 hours, the peak anticoagulant effect may be delayed 72 to 96 hours, which may explain the increased incidence of total DVTs and the comparable prevention of proximal DVT in the warfarin group. To address this problem, some warfarin regimens are started the evening before surgery.
Enoxaparin and warfarin were given for approximately 9 days. Current practice in knee arthroplasty is a stay of 4 to 5 days after surgery. Therefore, to apply these study results to practice would require 4 to 5 days of home treatment.
The cost of enoxaparin, 30 mg every 12 hours, is approximately U.S. $24 per day, plus the cost of hemoglobin monitoring and nursing personnel to give injections. The cost of warfarin is approximately U.S. $0.05 per tablet; prothrombin time and hemoglobin monitoring must also be taken into consideration.
Enoxaparin clearly deserves a place in DVT prophylaxis after knee arthroplasty. Its role, however, will be affected by current pricing and issues of feasibility in the clinical setting.
Leon Pedell, MD
William Beaumont HospitalRoyal Oak, Michigan, USA