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


Therapeutics

At least 2 low-molecular-weight heparins are more effective and safer than standard unfractionated heparin

ACP J Club. 1995 Nov-Dec;123:61. doi:10.7326/ACPJC-1995-123-3-061


Source Citation

Lensing AW, Prins MH, Davidson BL, Hirsh J. Treatment of deep venous thrombosis with low-molecular-weight heparins. A meta-analysis. Arch Intern Med. 1995 Mar 27;155: 601-7.


Abstract

Objective

To compare the efficacy and safety of low-molecular-weight heparin (LMWH) with standard unfractionated heparin (SH) for the initial treatment of deep venous thrombosis (DVT).

Data Sources

English-language studies were identified through MEDLINE (1984 to 1994) using the terms heparin, low-molecular-weight heparin, and venous thromb* (various endings); Current Contents-Clinical Practice; lists of conference abstracts; bibliographies of relevant papers; and contact with authors and experts.

Study Selection

Studies were selected if they compared LMWH and SH adjusted to obtain a therapeutic range for the initial treatment of DVT, used an objective test to diagnose DVT, had an independent outcome assessment, used currently accepted doses of heparin, and were the fullest or most recent report of a trial.

Data Extraction

Numbers of patients; administration route, dose, and type of heparin; international normalized ratio ranges; DVT complications including bleeding, recurrence, and mortality; and venographic findings before and after treatment.

Main Results

19 trials were identified, and 10 met the inclusion criteria. Fraxiparine, Logiparin, Fragmin, and Clexane LMWH were studied. Combined data showed that patients who received LMWH, compared with patients receiving SH, had fewer thromboembolic complications (3.1% vs. 6.6%; {95% CI for the 3.5% absolute risk reduction [ARR], 0.9% to 6.1%; P = 0.008; relative risk reduction [RRR], 53%; number needed to treat [NNT], 29; CI, 16 to 110}*), a lower rate of major bleeding complications (0.9% vs. 3.2%; {CI for the 2.3% ARR, 0.7% to 4.0%; P = 0.003; RRR, 68%; NNT, 44; CI, 25 to 125}*), lower total mortality (3.9% vs. 7.1%; {CI for the 3.2% ARR, 0.6% to 6.1%; P < 0.02; RRR, 47%; NNT, 31; CI, 16 to 181}*), and lower mortality for patients with cancer (12.1% vs. 27.7%; CI for the 15.6% ARR, 4.2% to 26.9%; P = 0.008; RRR, 56%; NNT 6; CI, 4 to 24}*). 63% of patients receiving LMWH and 52% of patients receiving SH had a reduction in thrombus size (P = 0.001). Fraxiparine showed a reduction in thromboembolic complications (P < 0.04), Logiparin showed a reduction in bleeding (P < 0.04) and mortality (P = 0.049), and Fraxaparine (P = 0.001) and Clexane (P = 0.003) showed more patients with a reduction in thrombus size.

Conclusion

Carefully controlled LMWH compared with SH for the initial treatment of deep venous thrombosis shows reductions in thrombus size, recurrences, major bleeding complications, and mortality in all patients and patients with cancer.

Source of funding: Not stated.

For article reprint: Dr. A. W. Lensing, Academic Medical Center H-2, Meibergdroof 9, 1105 AZ Amsterdam, the Netherlands, FAX 31-20-697-1438.

*Numbers calculated from data in article.


Commentary

The use of LMWH in the prevention and treatment of thromboembolic disease has received increased support. LMWH is injected subcutaneously once or twice daily, and no blood test is required to monitor its safety. Although LMWH is more expensive than SH, its potential use in managing patients with acute DVT in the ambulatory setting could result in substantial cost savings and improved patient convenience.

This well-designed meta-analytic overview compares important treatment outcomes and complications in persons receiving LMWH with those in persons receiving therapeutic doses of SH for acute DVT. In aggregate, fewer symptomatic thromboembolic complications, less bleeding, and lower mortality rates occur in patients receiving LMWH. 4 LMWHs were studied. In subanalysis, the 2 Fraxaparine trials and the single Logiparin trial were significantly linked to treatment benefits. Because the effects of the LMWHs may differ, the authors appropriately urge that additional randomized controlled trials be done for the other LMWHs.

The overview by Lensing and colleagues supports the previous observation that the antithrombotic effect of LMWHs outweighs the hemorrhagic effects of these agents. It extends the indications for LMWH as the initial treatment for acute DVT. A previous overview showed the efficacy of LMWH compared with SH in the prevention of DVT and pulmonary embolism in patients having hip arthroplasty (1). A recent trial suggests that heparin-associated thrombocytopenia is less likely with LMWH (2). We await further trials to determine the safety of treating acute DVT in the ambulatory setting.

Brian P. Schmitt, MD
Northwestern University Medical School Chicago, Illinois, USA