Correspondence

Enoxaparin as Prophylaxis against Thromboembolism after Total Hip Replacement

N Engl J Med 1997; 336:585-586February 20, 1997

Article

To the Editor:

We are concerned about the report of Bergqvist et al. (Sept. 5 issue)1 and the implications it may have for patient care. They reported that among patients who had total hip arthroplasty, the rate of venography-confirmed deep-vein thrombosis was substantially reduced in those who had continuing prophylaxis with the low-molecular-weight heparin enoxaparin after hospital discharge, compared with a control group that received enoxaparin prophylaxis only while hospitalized. Although we do not question the validity of these findings, we do challenge the clinical significance of the results. Venography-confirmed deep-vein thrombosis after orthopedic surgery is an excellent end point for determining the relative efficacy of antithrombotic agents, since a high rate of events is observed. However, the clinical significance of these largely asymptomatic thrombi is uncertain. If untreated, how many will lead to thromboembolic complications?

Before a strategy of extending the duration of prophylaxis after joint arthroplasty beyond discharge from the hospital is developed, possibly increasing the risk of bleeding, we feel that large, randomized, controlled trials are required to determine whether prolonging prophylaxis reduces the rate of clinically important venous thromboembolic complications, such as symptomatic deep-vein thrombosis and pulmonary embolism. Venography, because of its high sensitivity to small deep-vein thrombi, may not be the appropriate test to diagnose symptomatic deep-vein thrombosis in such studies.

David R. Anderson, M.D.
Michael Gross, M.D.
K. Sue Robinson, M.D.
Queen Elizabeth II Health Sciences Centre, Halifax, NS B3H 1V8, Canada

Philip S. Wells, M.D.
Ottawa Civic Hospital, Ottawa, ON K1Y 4E9, Canada

1 References

1. 1

   Bergqvist D, Benoni G, Bjorgell O, et al. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996;335:696-700
   Full Text | Web of Science | Medline

To the Editor:

I found the article by Bergqvist et al. to be a welcome documentation of the prolonged risk of venous thromboembolism after total hip replacement. Readers should note some important features of this paper, however. In the study, enoxaparin was given subcutaneously once every 24 hours in a 40-mg dose. Current marketing suggests giving 30 mg every 12 hours; in the United States, enoxaparin can be purchased only in 30-mg prefilled syringes.

In addition, the cost of 40 mg of enoxaparin, administered subcutaneously each day, would be 300 times that of daily warfarin sodium, a most acceptable alternative for prophylaxis against venous thromboembolism in outpatients ($15.00 vs. $0.05 per day). Although monitoring warfarin sodium would require an occasional measurement of the prothrombin time, the expense of this would be far less than that of daily injections.

Leon Pedell, M.D.
William Beaumont Hospital, Royal Oak, MI 48073

Author/Editor Response

Dr. Bergqvist replies:

To the Editor: In one respect, our study does not differ from many other studies of thromboprophylaxis — we do not fully know the clinical relevance of asymptomatic deep-vein thrombosis. Besides our study, three additional studies have arrived at similar conclusions — that prolonged prophylaxis does significantly reduce the frequency of venographically diagnosed deep-vein thrombosis after hip arthroplasty.1 Obviously, there is much that is still unknown: the clinical relevance of late thrombosis for pulmonary embolism and the post-thrombotic syndrome, the reproducibility of our findings in a routine clinical setting, economic implications, and detailed definition of risk groups, among others. An indication that prolonged prophylaxis may be of benefit is the reduction in the rate of symptomatic deep-vein thrombosis in our study from 8 to 2 percent and in the study by Planes et al.2 from 8 to 3 percent. However, in our paper we did not recommend the widespread use of prolonged prophylaxis until more information is obtained. In the past, most studies of thromboprophylaxis focused on clinical end points, then attention switched to “objective” diagnostic methods such as venography and the fibrinogen-uptake test, and now we have returned to studying clinical end points.

I have no comments regarding the dosage question raised by Dr. Pedell. The dose we used is the common regimen in Europe.

David Bergqvist, M.D., Ph.D.
Academic Hospital, S-751 85 Uppsala, Sweden

2 References

1. 1

   Bergqvist D. The postdischarge risk of venous thromboembolism after hip replacement: the role of prolonged prophylaxis. Drugs 1996;52:Suppl 7:55-59
   CrossRef | Web of Science | Medline

2. 2

   Planes A, Vochelle N, Darmon JY, Fagola M, Bellaud M, Huet Y. Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo. Lancet 1996;348:224-228
   CrossRef | Web of Science | Medline