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


Therapeutics

Review: Low-molecular weight heparin reduces the risk for developing deep-vein thrombosis and pulmonary embolism in patients having orthopedic surgery

ACP J Club. 1992 Nov-Dec;117:77. doi:10.7326/ACPJC-1992-117-3-077


Source Citation

Nurmohamed MT, Rosendaal FR, B├╝ller HR, et al. Low-molecular-weight heparin versus standard heparin in general and orthopaedic surgery: a meta-analysis. Lancet. 1992 Jul 18;340:152-6.


Abstract

Objective

To compare the efficacy and safety of low-molecular-weight heparin (LMWH) and standard heparin (SH) for the prevention of deep-vein thrombosis in orthopedic and general surgery.

Data sources

Studies were identified using MEDLINE (1984 to April 1991), Current Contents, lists of conference abstracts, and bibliographies of relevant papers.

Study selection

Randomized studies were selected if they reported data from patients having general surgery (abdominothoracic or gynecologic) or orthopedic surgery (elective or traumatic hip surgery) where LMWH was compared with unfractionated heparin, both given in currently recommended doses. All patients having general surgery were required to have had 125I-fibrinogen leg scanning, and, in orthopedic surgery, routine venography.

Data extraction

2 independent observers assessed each article for quality and extracted the rates of deep-vein thrombosis, fatal and nonfatal pulmonary embolism, total mortality, and major bleeding using predefined criteria.

Main results

The 17 general surgery articles selected included 6878 patients, and the 6 orthopedic surgery articles included 1294 patients. For all trials the combined relative risk (RR) for developing deep-vein thrombosis while taking LMWH compared with taking SH was 0.74 (95% CI 0.65 to 0.86) and the RR for pulmonary embolism (fatal and nonfatal) was 0.43 (CI 0.26 to 0.72). The groups did not differ for incidence of major bleeding (RR 0.98, CI 0.69 to 1.40). 20 patients in the LMWH group died compared with 24 in the SH group.

Analysis of the 13 papers that had the strongest methodology showed a smaller benefit of LMWH in deep-vein thrombosis risk-reduction (RR for general surgery 0.91 [CI 0.68 to 1.23]; RR for orthopedic surgery 0.75 [CI 0.56 to 0.99]) with nonsignificant trends for reduction of pulmonary embolism and increase of major bleeding. Using these data, LMWH would have to be given to 14 patients having orthopedic surgery and 71 having general surgery to prevent 1 additional episode of deep-vein thrombosis.

Conclusions

Risks for developing deep-vein thrombosis and pulmonary embolism are less with low-molecular-weight heparin than standard heparin. A large absolute reduction in these risks is shown when patients having orthopedic surgery are given low-molecular-weight heparin. For patients having general surgery the benefits of low-molecular-weight heparin are less clear.

Source of funding: In part, the Royal Netherlands Academy of Arts and Sciences.

For article reprint: Dr. M.T. Nurmohamed, Centre for Haemostasis, Thrombosis, Atherosclerosis and Inflammation Research, F4-131, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.


Commentary

Recently, several LMWH preparations have been developed for both treatment and prevention of deep-vein thrombosis, and reports suggest that LMWH provides superior effectiveness and safety compared with SH (1). It is reasonable, therefore, to do a meta-analysis to show whether LMWH provides advantages over SH and, if so, what reliable estimates of the benefits are. The study by Nurmohamed and colleagues is a sound meta-analysis, and it provides estimates of the relative risks and benefits of LMWH used for prevention of venous thrombosis in orthopedic and general surgery. LMWH, in patients having orthopedic surgery, shows risk reductions of approximately 25% in the incidence of deep-vein thrombosis and approximately 50% to 60% in the incidence of pulmonary embolism with little increase in bleeding. Studies with strong methods were unable to show a difference in the incidence of venous thrombosis in patients having general surgery, and this may be a type 2 error: because the absolute rate of deep-vein thrombosis in patients treated with SH is low, many patients must be studied to show a significant difference with LMWH. The inaccuracy of fibrinogen leg scanning for detecting deep-vein thrombosis probably compounds the problem.

As LMWH becomes available in North America, its relatively high cost, compared with SH, will be a key factor in its use. Because the evidence is convincing that LMWH shows a significant risk reduction in the incidence of deep-vein thrombosis in major hip surgery, it may be widely used for these patients. For general surgery, because there is a lack of evidence that LMWH in comparison with SH provides a significant or clinically important risk reduction in the incidence of deep-vein thrombosis, LMWH may be less widely used.

Jeff Ginsberg, MD
McMaster UniversityHamilton, Ontario, Canada


Reference

1. Hull RD, Raskob GE, Pineo GF, et al. Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal vein thrombosis. N Engl J Med. 1992;326:975-82.