LMWHs Appear to be as Safe and Effective as Unfractionated Heparin

Abstract & Commentary

Synopsis: Low molecular weight heparins reduced the mortality rates over 3-6 months of patient follow-up (odds ratio 0.71; P = 0.02).

Source: Gould MK, et al. Ann Intern Med 1999;130:800-809.

Low molecular weight heparins (LMWHS) simplify the treatment of acute deep venous thrombosis because they may be administered subcutaneously once or twice daily, without the need for laboratory monitoring or dose adjustment in most cases. A critical clinical issue is whether this more convenient therapy is as safe and effective as treatment with conventional unfractionated heparin.

Gould and colleagues completed a carefully orchestrated meta-analysis to incorporate the most recent data from clinical trials to resolve discrepancies among previous reviews. Only 11 of 37 studies met inclusion criteria for the three major outcomes considered (mortality rates over 3-6 months, major bleeding complications, and prevention of recurrences).

LMWH reduced the mortality rates over 3-6 months of patient follow-up (odds ratio, 0.71; P = 0.02). Odds ratio favored LMWH over unfractionated heparin for major bleeding complications and for preventing thromboemboli recurrences but the absolute risk reductions were small and not statistically significant.

Comment by Ralph R. Hall, MD, FACP

This is an interesting and reassuring analysis. In the same issue of the Annals of Internal Medicine,1 Gould et al report a cost analysis that demonstrated that although the initial cost of LMWH was higher, this was partially offset by reduced costs for early complications. Additionally, if as few as 8% of the patients could be treated as outpatients, the costs were further reduced and cost savings were significant. The number of patients receiving outpatient treatment with LMWH will easily exceed 8% in most institutions.

In the same issue of the Annals of Internal Medicine,2 Milton C. Weinstein, PhD, the director of the Program on Economic Evaluation of Medical Technology at the Harvard School of Public Health, wrote an editorial on the cost of medical technology that should be read by all physicians interested in this area.

Weinstein states (in referring to the article on LMWH and an additional article,)3 "The explicit and scientific nature of these studies places an appropriate burden on persons who claim that these technologies are not good value for money and should not be paid for."

Weinstein points out that the reduction in death from 6.7% to 5.1% in the LMWH study is similar to the absolute reduction in death attributed to tissue plasminogen activators compared to streptokinase in the GUSTO trial (from 7.4% to 6.3%).4


    1. Gould MK, et al. Ann Intern Med 1999;130:789-799.

    2. Weinstein MC. Ann Intern Med 1999;130:859-860.

    3. Rosen AB. Ann Intern Med 1999;130:857-858.

    4. The GUSTO Investigators. N Engl J Med 1993;329: 673-682.

Which of the following statements regarding heparin use is correct?

    a. LMWH significantly reduces recurrences of venous thrombosis when compared to unfractionated heparin.
    b. LMWH produces more bleeding complications than unfractionated heparin.
    c. LMWH is not cost effective when compared to unfractionated heparin.
    d. LMWH was associated with less mortality than unfractionated heparin.