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Low-molecular-weight heparin versus warfarin for prevention of recurrent venous thromboembolism: a randomized trial |
Das S K, Cohen A T, Edmondson R A, Melissari E, Kakkar V V |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology Subcutaneous low-molecular-weight heparin (LMWH) versus warfarin for prevention of recurrent venous thromboembolism (DVT). The average molecular weight of LMWH was 4,000 to 6,000 daltons.
Economic study type Cost-effectiveness analysis.
Study population Male and female patients aged over 40 years with major deep vein thrombosis. Those patients with contraindication to anticoagulation therapy, allergy to iodine, pregnancy, inability to self-administer heparin, inability to attend for follow-up because of geographic inaccessibility, and serious concomitant disease likely to affect the evaluation of the treatment options, were excluded.
Setting Hospital and outpatient clinic. The study was carried out in London, UK.
Dates to which data relate The dates of the effectiveness and cost data were not stated.
Source of effectiveness data The estimates of the number of venographically proved recurrent DVTs, nonfatal pulmonary embolism and bleeding complications were derived from a single study.
Link between effectiveness and cost data The costing was undertaken prospectively on the same patient sample as that used in the effectiveness study.
Study sample No power calculations were reported. A total of 105 patients was included in the study, with 50 (24 male, average age 65.3 years (+/-14.9), 32% with a history of DVT) being allocated to the LMWH group and 55 (23 male, average age 58.6 years (+/- 16.4), 25% with a history of DVT) to the warfarin group.
Study design The study was a randomized controlled study. The duration of follow-up was three months. A restricted randomization list using permuted blocks, and obtained by means of computer-generated random numbers, was used to allocate patients between groups. Primary anticoagulation heparin therapy was administered to patients subcutaneously for 10 days. Then maintenance therapy, with either LMWH or the standard oral warfarin therapy, was given for 3 months. There was no loss to follow-up.
Analysis of effectiveness The analysis was based on intention to treat. The primary health outcomes were the number of venographically proved recurrent DVTs, nonfatal pulmonary embolism and bleeding complications.
Effectiveness results During the three months, four patients developed venographically proved recurrent DVT: three (6.8%) in the LMWH group and one (2.4%) in the control group (p=0.62). Nonfatal pulmonary embolism occurred in 2 patients in the LMWH group and 1 patient in the warfarin group. Thus, when all events were analysed together, 5 and 2 events developed, respectively (p=0.43). No bleeding complications appeared in the LMWH group and five minor haemorrhagic complications occurred in the warfarin group (p=0.06).
Clinical conclusions The fixed daily dose of LMWH and the adjusted dose of warfarin therapy were of similar efficacy in preventing recurrence of DVT.
Measure of benefits used in the economic analysis No summary benefit measure was used in the analysis and as such the benefits are considered to be the same as the outcome measures.
Direct costs Operating and overhead costs associated with the secondary therapy (i.e. excluding heparin) from initiation until three months after the start of therapy were included in the analysis. The quantities were reported separately from the prices. The quantity/cost analysis was performed from the perspective of the NHS. The price year was not reported. Since major complications did not occur, costs associated with complications were zero. The costs associated with heparin therapy were omitted because they were common to both strategies.
Sensitivity analysis No sensitivity analysis was performed.
Estimated benefits used in the economic analysis During the three months, four patients developed venographically proved recurrent DVT: three (6.8%) in the LMWH group and one (2.4%) in the control group (p=0.62). Nonfatal pulmonary embolism occurred in 2 patients in the LMWH group and 1 patient in the warfarin group. Thus, when all events were analysed together, 5 and 2 events developed, respectively (p=0.43). No bleeding complications appeared in the LMWH group and five minor haemorrhagic complications occurred in the warfarin group (p=0.06).
Cost results The total cost per patients in the LMWH and warfarin groups was, respectively, 357.5 and 1,272.0.
Synthesis of costs and benefits The LMWH option was shown to be the dominant strategy. An incremental analysis was not performed.
Authors' conclusions LMWH is a safe, efficacious therapy for the secondary prevention of recurrent DVT relative to (the standard) warfarin therapy.
CRD COMMENTARY - Selection of comparators The reason for the choice of comparator is clear. Warfarin was reported as the standard secondary treatment of patients with major deep vein thrombosis. However, warfarin therapy is associated with several problems (e.g. fatal haemorrhage, strict laboratory control, and congenital anomalies if administrated during pregnancy) which can be avoided by the use of LMWH therapy. You, as a user of this database, should consider whether these are widely used health technologies in your setting.
Validity of estimate of measure of benefit The measure of benefit is likely to be valid, given the study design used, and the analyses performed in terms of the differences between groups in relevant clinical and demographic characteristics. The sample size, however, appears to have resulted in low power for the statistical tests applied to the results. The authors did not state the date when the trial was performed.
Validity of estimate of costs The cost analysis lacked some detail in terms of the methodology employed, although broad quantities of resource use were given. Neither the price date nor dates associated with other data were provided by the authors.
Other issues The conclusions reached by the authors were partly justified given the uncertainties in the data. The generalisability of the study results was not properly addressed. However, appropriate comparisons were made with other studies. Results do not appear to have been presented selectively.
Implications of the study It remains to be seen if using LMWH throughout the acute phase and possibly a higher dose of LMWH for the chronic phase can lead to improved efficacy and still maintain safety.
Source of funding Supported by a grant from the Thrombosis Research Trust.
Bibliographic details Das S K, Cohen A T, Edmondson R A, Melissari E, Kakkar V V. Low-molecular-weight heparin versus warfarin for prevention of recurrent venous thromboembolism: a randomized trial. World Journal of Surgery 1996; 20(5): 521-527 Indexing Status Subject indexing assigned by NLM MeSH Aged; Female; Heparin, Low-Molecular-Weight /therapeutic use; Humans; Infant, Newborn; Male; Middle Aged; Prospective Studies; Recurrence; Thromboembolism /prevention & Warfarin /therapeutic use; control AccessionNumber 21996000672 Date bibliographic record published 31/01/1999 Date abstract record published 31/01/1999 |
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