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Therapeutics

Low-molecular-weight heparin at home was as effective as unfractionated heparin in the hospital in proximal DVT

ACP J Club. 1996 July-Aug;125:3. doi:10.7326/ACPJC-1996-125-1-003


Source Citation

Levine M, Gent M, Hirsh J, et al. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med. 1996 Mar 14;334:677-81. [PubMed ID: 8594425]


Abstract

Objective

To compare the effectiveness of subcutaneous low-molecular-weight heparin (LMWH) administered primarily at home with continuous intravenous standard heparin administered in the hospital in patients with deep venous thrombosis (DVT).

Design

Randomized controlled trial with 90-day follow-up.

Setting

15 hospitals in Canada.

Patients

500 consecutive patients (mean age 58 y, 60% men) with acute proximal DVT (thrombosis in the popliteal vein or a more proximal vein) confirmed by venography or duplex ultrasonography. Exclusion criteria were ≥ 2 previous episodes of DVT or pulmonary embolism; active bleeding, active peptic ulcer disease, or a familial bleeding disorder; concurrent symptomatic pulmonary embolism; treatment for > 48 hours with standard heparin for the DVT qualifying them for the study; an inability to be treated with LMWH because of a coexisting condition or the likelihood of noncompliance; an inability to make follow-up visits; the presence of a known deficiency of antithrombin III, protein C, or protein S; or pregnancy. No patients were lost to follow-up.

Intervention

247 patients were allocated to LMWH, 1 mg of enoxaparin (Lavenox, Rhône-Poulenc Rorer, Montreal, Quebec) per kilogram of body weight subcutaneously twice daily, administered primarily at home. No laboratory monitoring was done in this group. 253 patients were allocated to intravenous standard heparin, a bolus dose of 5000 units intravenously followed by a continuous infusion of 20 000 units of standard heparin in 500 mL of a 5% dextrose solution with 32 mL administered per hour, in the hospital. The infusion rate was adjusted to keep activated partial-thromboplastin time in the targeted therapeutic range of 60 to 85 seconds. All patients received warfarin starting on the second day (targeted international normalized ratio 2.0 to 3.0).

Main outcome measures

Recurrent thromboembolism, major bleeding, and days in the hospital.

Main results

The mean duration of study treatment was 5.8 days in the LMWH group and 5.5 days in the standard heparin group. 13 patients receiving LMWH had symptomatic recurrent thromboembolism compared with 17 patients assigned to standard heparin (P = 0.57) (Table). 5 patients assigned to LMWH had major hemorrhagic complications compared with 3 patients assigned to standard heparin (P = 0.50) (Table). After randomization, the mean time spent in the hospital by the patients assigned to LMWH was 1.1 days compared with 6.5 days by the patients assigned to standard heparin. 120 patients (49%) assigned to LMWH were never hospitalized.

Conclusion

Low-molecular-weight heparin administered primarily at home was as effective and safe as unfractionated heparin administered in the hospital in patients with acute proximal deep venous thrombosis.

Source of funding: Not available.

For article reprint: Dr. M. Levine, Hamilton Regional Cancer Centre, 699 Concession Street, Hamilton, Ontario L8V 5C2, Canada.


Table. Low-molecular-weight heparin at home (LMWH) vs intravenous standard heparin in the hospital in proximal DVT*

Outcomes at 90 d LMWH Heparin RRR (95% CI) NNT
Recurrent thrombeombolism 5.3% 6.7% 22% (-56 to 61) Not significant
RRR (CI) NNH
Major hemorrhage 2% 1.2% 71% (-54 to 541) Not significant

*Abbreviations defined in Glossary. RRR, RRI, NNT, NNH, and CI calculated from data in article.


Commentary

Low molecular heparin at home was as effective as unfractionated heparin in the hospital in proximal DVT

Anticoagulant therapy is the treatment of choice for most patients with DVT. Patients are usually treated in the hospital with intravenous unfractionated heparin followed by oral anticoagulants for at least 3 months.

LMWH preparations compared with standard heparin have a longer plasma half-life, a less variable anticoagulant response, and a more favorable antithrombotic-to-hemorrhage ratio (1). LMWH compounds have been found to be safe and effective in the prophylaxis of venous thromboembolism (2) and in the treatment of acute proximal DVT (3, 4).

These 2 recent studies by Levine and Koopman and their colleagues provide further evidence that LMWH given at home is safe and effective for initial treatment of acute proximal DVT in selected patients. These 2 multinational, randomized studies, although unblinded, were carefully done to minimize bias. Although 2 different LMWH compounds were used, the results were similar. Because each LMWH compound is distinct in its activity (1), multiple, large clinical trials are needed.

Clearly, reducing hospitalization is an increasingly important part of patient management. Both of these studies have shown that LMWH given at home without laboratory monitoring is a cost-effective initial treatment for acute proximal DVT. The incidence of severe hemorrhagic events or life-threatening pulmonary embolism during the initial treatment was exceedingly low in both studies. The need for hospitalization to monitor patients, therefore, does not seem warranted.

In the study by Levine and colleagues, approximately two thirds of the patients with acute proximal DVT were excluded; 40% were excluded because of their inability to receive outpatient therapy with LMWH because of associated coexisting conditions (e.g., cancer, infection, or stroke).

The results of these 2 studies provide more convincing evidence that many patients with acute proximal DVT can be safely treated as outpatients. Those patients who have suspected pulmonary embolism or who are at higher risk for bleeding complications (e.g., coagulopathy, liver disease) should receive standard intravenous heparin in the hospital.

Scott A. Kolander, MD
Mercer Medical CenterTrenton, New Jersey, USA


References

1. Hirsh J, Levine MN. Low molecular weight heparin. Blood. 1992;79:1-17.

2. Nurmohamed MT, Rosendaal FR, Büller HR, et al. Low-molecular-weight heparin versus standard heparin in general and orthopedic surgery: a meta-analysis. Lancet. 1992;340:152-6.

3. Lensing AW, Prins MH, Davidson BL, et al. Treatment of deep vein thrombosis with low molecular weight heparins: a meta-analysis. Arch Intern Med. 1995;155:601-7.

4. Leizorovicz A, Simonneau G, Decousus H, Boissel JP. Comparison of efficacy and safety of low-molecular-weight-heparins and unfractionated heparin in initial treatment of deep venous thrombosis: a meta-analysis. BMJ. 1994;309:299-304.


Updated Commentary

Subsequent studies have provided further evidence that venous thromboembolism can be safely treated with low-molecular-weight heparin. 4 studies (5-8) have included patients with pulmonary embolism, who had been excluded in previous trials. LMWH was as safe and effective as intravenous, adjusted-dose unfractionated heparin.

A meta-analysis of 11 randomized, controlled trials of LMWH compared with unfractionated heparin for treatment of acute DVT found that LMWH was safe and effective for treatment of DVT (9). In 3 trials, there was a trend for lower mortality rates with patients treated with LMWH; however, the exact mechanism for this finding is unclear.

With increasing emphasis on reducing health care costs, treatment of both DVT and pulmonary embolism with LMWH may allow for shortened hospital stays and for selected patients to be treated as outpatients.

Scott A. Kolander, MD
Mercer Medical CenterTrenton, New Jersey, USA

5. Kovacs MJ, Anderson D, Morrow B, et al. Outpatient treatment of pulmonary embolism with dalteparin. Thromb Haemost 2000;83:209-11.

6. Simonneau G, Sors H, Charbonnier B, et al., for the THESEE Study Group. A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. N Engl J Med. 1997;337:663-9.

7. The Columbus Investigators. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med. 1997;337:657-62.

8. Wells PS, Kovacs MJ, Bormanis J, et al. Expanding eligibility for outpatient treatment of deep venous thrombosis and pulmonary embolism with low-molecular-weight heparin: a comparison of patient self-injection with homecare injection. Arch Intern Med. 1998;158:1809-12.

9. Gould MK, Dembitzer AD, Doyle RL, Hastie TJ, Garber AM. Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. Ann Intern Med. 1999;130:800-9.