Toronto — A new study led by Canadian researchers may have implications for the way physicians treat blood clots in the deep veins of the legs or the lungs of patients.
The study, published in Wednesday's issue of the Journal of the American Medical Association, compared two drugs used to treat deep vein thrombosis, or DVT, and found that the cheaper one was as effective and safe as the more expensive therapy.
The study also questions the need for the current practice of coagulation monitoring, known as APTT, during treatment with the cheaper drug. Patients being monitored have to be in a hospital.
Researchers followed patients in six university-affiliated clinical centres in Canada and New Zealand from September 1998 to February 2004.
About half the patients were given the cheaper drug — unfractionated heparin — while the rest were given the more expensive low-molecular-weight heparin. Both drugs were given twice daily by subcutaneous injection (beneath the skin).
Dr. Clive Kearon, the lead author and a professor of medicine at McMaster University in Hamilton, Ont., said the more expensive therapy is the most commonly used treatment of DVT in Canada.
Today, when unfractionated heparin is used, it is usually given through intravenous injection along with APTT monitoring, which doctors use to continually adjust the dose of heparin being injected.
“The reason that we did the study in the first place was because there was evidence from previous studies suggesting that such monitoring was not necessary if you were giving currently recommended doses of (unfractionated) heparin,” said Dr. Kearon.
“(Our findings) allow you to give unfractionated heparin by injection twice a day without doing the (APTT) monitoring and that allows you to give it to outpatients.”
Dr. Bruce Ritchie, a hematologist and associate professor at the University of Alberta, has been watching the treatment of DVT evolve over more than two decades and calls Dr. Kearon's study “fabulous.”
Dr. Ritchie said when treatment using low-molecular-weight heparin came around in the mid-1990s it was a big deal because it got patients out of hospital beds at a time when overcrowding was happening nationwide.
“If we can continue to do it but with a cheaper drug, then that's tremendous,” he said.
Dr. Kearon said the cost difference for the two drugs is a big factor in the United States, where low-molecular-weight heparin would cost $712 (U.S.) for a six-day treatment, compared with $37 for the unfractionated heparin. In Canada, low-molecular-weight heparin is only about two or three times as much.
But Dr. Ritchie said cost is still an issue here. A woman who gets low-molecular-weight heparin for the duration of her pregnancy winds up with a cost approaching $10,000 that she, or her drug plan, must cover.
Unfractionated heparin, on the other hand, is “about the same price as Kool-Aid,” he said.
One of the exciting things for Dr. Ritchie about the study is that it challenges the paradigm of APTT being a valuable tool.
“It is really a poor test, but a whole culture of medicine has come to rely on it,” he said.
But Dr. Kearon stressed that while the findings do challenge the need for APTT monitoring, the evidence is not enough to say it's no longer needed.
“It questions it but that's about as far as it goes,” he said.
Although satisfied with the findings, Dr. Kearon said one drawback may be that the size of the study might not have been big enough for the results to drastically change the way DVT is treated.
Recurrent thromboembolism occurred in 3.8 per cent of the 345 patients in the unfractionated heparin group, and in 3.4 per cent of the 352 patients in the low-molecular weight heparin group.
An editorial that accompanies the study says the results must be replicated using a double-blind trial design — in which patients and physicians don't know which anticoagulant the patient is receiving — before the approach can be widely adopted in clinical practice.
“If the patient can be observed very closely, this treatment regimen might be used very cautiously in carefully selected patients who prefer outpatient treatment of venous thromboembolism and cannot afford the expense of low-molecular-weight heparin,” writes Dr. Jeffrey Carson of the University of Medicine & Dentistry of New Jersey.
Dr. Kearon said he would welcome a second study.
Another issue Dr. Ritchie raised is with the drugs themselves.
“The low-molecular-weight heparins have been used long term with good success,” he said. “One of the problems with the unfractionated heparin is it's associated with osteoporosis (through increased bone loss).”
The study was funded in part by the Heart and Stroke Foundation, which Dr. Kearon said makes it only one of two studies on these drugs not to be industry-funded.
He said this is important because without public and private-donor funding, it would not have been possible for researchers “to evaluate the possibility of a cheaper way to treat venous thrombosis.”
