Use of a New Form of the Blood Thinner Heparin Outside the Hospital To Prevent Blood Clots after Hip or Knee Replacement

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The summary below is from the full report titled " Ardeparin Sodium for Extended Out-of-Hospital Prophylaxis against Venous Thromboembolism after Total Hip or Knee Replacement. A Randomized, Double-Blind, Placebo-Controlled Trial." It is in the 6 June 2000 issue of Annals of Internal Medicine (volume 132, pages 853-861). The authors are J.A. Heit, C.G. Elliott, A.A. Trowbridge, B.F. Morrey, M. Gent, and J. Hirsh, for the Ardeparin Arthroplasty Study Group.

What is the problem and what is known about it so far?

Blood clots can form in the deep veins of the leg, a condition called "deep venous thrombosis," as a complication of hip or knee replacement surgery. These clots can break off and travel through the bloodstream to the lungs, shutting off some of the lung's circulation, a condition called "pulmonary embolism." Giving patients blood thinners in the hospital after joint replacement surgery can prevent deep venous thrombosis and pulmonary embolism. However, it remains unknown how long the blood thinners should be continued. Commonly used blood thinners are standard heparin (usually given through an intravenous line), warfarin (given by mouth), or low-molecular-weight heparin (a new form of the drug given by injection under the skin). Low-molecular-weight heparin is more convenient than regular heparin because it can be given once daily and, unlike heparin and warfarin, does not require frequent blood tests to adjust the dose.

Why did the researchers do this particular study?

To find out whether giving joint replacement patients low-molecular-weight heparin for 6 weeks after they go home from the hospital prevents blood clots.

Who was studied?

1195 adults who had total hip or knee replacement surgery and who had completed 4 to 10 days of low-molecular-weight heparin before leaving the hospital.

How was the study done?

Just before patients left the hospital, the researchers randomly assigned them to receive a daily injection of ardeparin sodium (a particular type of low-molecular-weight heparin) or placebo (a substance that looked like the ardeparin but contained no active ingredients). The study patients continued the injections for 6 weeks after they went home. The researchers then followed patients for 12 weeks to see who developed symptoms of thromboembolism or died. Patients who had symptoms of thromboembolism underwent tests to confirm the diagnosis.

What did the researchers find?

Of the 607 patients who got ardeparin, 9 (1.5%) suffered thromboembolism or died compared with 12 of the 588 patients who got placebo (2.0%). Statistical analysis showed that these rates were not significantly different than what one might expect from chance alone.

What were the limitations of the study?

The researchers combined the findings in patients who had knee and hip replacement surgery, so they may have missed a benefit that applied to only one type of surgery. In addition, the study was not large enough to completely rule out a small benefit from ardeparin therapy.

What are the implications of the study?

Without treatment with blood thinner after leaving the hospital, about 2 of every 100 patients will experience thromboembolism or die following joint replacement surgery. Continuing ardeparin for 6 weeks after hospitalization is unlikely to substantially reduce the occurrence of this complication.