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Low-Molecular-Weight Heparins Compared with Unfractionated Heparin for Treatment of Acute Deep Venous Thrombosis: A Cost-Effectiveness Analysis

Michael K. Gould, MD, MSc; Anne D. Dembitzer, MD; Gillian D. Sanders, PhD; and Alan M. Garber, MD, PhD
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From Veterans Affairs Palo Alto Health Care System, Palo Alto, California; and Stanford University Medical Center and Stanford University, Stanford, California.

Ann Intern Med. 1999;130(10):789-799. doi:10.7326/0003-4819-130-10-199905180-00002
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Background: Low-molecular-weight heparins are effective for treating venous thrombosis, but their cost-effectiveness has not been rigorously assessed.

Objective: To evaluate the cost-effectiveness of low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis.

Design: Decision model.

Data Sources: Probabilities for clinical outcomes were obtained from a meta-analysis of randomized trials. Cost estimates were derived from Medicare reimbursement and other sources.

Target Population: Two hypothetical cohorts of 60-year-old men with acute deep venous thrombosis.

Time Horizon: Patient lifetime.

Perspective: Societal.

Intervention: Fixed-dose low-molecular-weight heparin or adjusted-dose unfractionated heparin.

Outcome Measures: Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. An inpatient hospital setting was used for the base-case analysis. Secondary analyses examined outpatient treatment with low-molecular-weight heparin.

Results of Base-Case Analysis: Total costs for inpatient treatment were $26 516 for low-molecular-weight heparin and $26 361 for unfractionated heparin. The cost of initial care was higher in patients who received low-molecular-weight heparin, but this was partly offset by reduced costs for early complications. Low-molecular-weight heparin treatment increased quality-adjusted life expectancy by approximately 0.02 years. The incremental cost-effectiveness of inpatient low-molecular-weight heparin treatment was $7820 per QALY gained. Treatment with low-molecular-weight heparin was cost saving when as few as 8% of patients were treated at home.

Results of Sensitivity Analysis: When late complications were assumed to occur 25% less frequently in patients who received unfractionated heparin, the incremental cost-effectiveness ratio increased to almost $75 000 per QALY gained. When late complications were assumed to occur 25% less frequently in patients who received low-molecular-weight heparin, this treatment resulted in a net cost savings. Inpatient low-molecular-weight heparin treatment became cost saving when its pharmacy cost was reduced by 31% or more, when it reduced the yearly incidence of late complications by at least 7%, when as few as 8% of patients were treated entirely as outpatients, or when at least 13% of patients were eligible for early discharge.

Conclusions: Low-molecular-weight heparins are highly cost-effective for inpatient management of venous thrombosis. This treatment reduces costs when small numbers of patients are eligible for outpatient management.


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Figure 1.
The cost-effectiveness decision model.DVTUFHLMWHPE

At left, a square node represents the decision to treat acute deep venous thrombosis ( ) with either unfractionated heparin ( ) or low-molecular-weight heparin ( ). In the primary analysis, low-molecular-weight heparin treatment always occurred in an inpatient hospital setting. In the secondary analysis, some patients were eligible for early discharge or outpatient treatment, as indicated by the first round uncertainty node. All patients were at risk for early complications. Probabilities for early complications depended on the type of treatment received. Two early complications, major bleeding and pulmonary embolism ( ), were potentially fatal. All patients who did not develop a fatal early complication were at risk for a fatal or nonfatal late complication. Late complications included episodes of recurrent deep venous thrombosis and pulmonary embolism that occurred more than 6 months after the initial episode of deep venous thrombosis, mild and severe postphlebitic syndrome, superficial venous thrombosis, cellulitis, venous ulcer, varicose veins, stasis dermatitis, and deep venous insufficiency. The diamond-shaped nodes at the end of each path in the decision tree represent both the costs and the health effects associated with the full sequence of events in that particular path.

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Figure 2.
Tornado diagram showing the results of univariate sensitivity analyses.dashed vertical lineQALY

The solid vertical line represents the incremental cost-effectiveness of inpatient treatment with low-molecular-weight heparin relative to treatment with unfractionated heparin when all variables were set at their baseline value. Horizontal bars indicate the range in incremental cost-effectiveness ratios obtained by setting each variable at the lower and upper limit of its range and holding all other variables constant at their baseline value. Incremental cost-effectiveness ratios less than $0 ( ) indicate that treatment with low-molecular-weight heparin is cost saving. The cost-effectiveness of inpatient treatment with low-molecular-weight heparin was sensitive to only one variable: the effectiveness in preventing late complications. When other model variables were tested over a wide range of values, the cost-effectiveness ratio for inpatient treatment with low-molecular-weight heparin was always less than $25 000 per quality-adjusted life-year ( ) gained.

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Figure 3.
Results of multivariate sensitivity analysis.circlesdiamondstrianglesQALY

Each solid line indicates the incremental cost-effectiveness of inpatient treatment with low-molecular-weight heparin relative to unfractionated heparin at various levels of pharmacy costs for low-molecular-weight heparin. The middle line ( ) represents baseline assumptions about the effectiveness of low-molecular-weight heparin in preventing early complications. The upper ( ) and lower ( ) lines represent the incremental cost-effectiveness of low-molecular-weight heparin treatment at its lower and upper limits of effectiveness in preventing early complications. Vertical bars represent the effect of varying the cost of treating early complications by ±25%. A negative cost-effectiveness ratio indicates that low-molecular-weight heparin is a cost-saving strategy. The cost-effectiveness ratio for inpatient treatment with low-molecular-weight heparin was almost always less than $25 000 per quality-adjusted life-year ( ) except when low-molecular-weight heparin was assumed to be at the lower limit of effectiveness in preventing early complications and the pharmacy cost was $105 (125% of the baseline estimate) or greater.

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