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Wednesday, February 26, 2003Until now, there has been no proven long-term therapy that is safe for high-risk patients. When a clot develops, people are usually given warfarin for three to six months, but then the drug is stopped, because it increases the risk of severe bleeding. Without warfarin, however, almost a third of the patients will form another clot within eight years. The new study has found that after a few months of standard treatment with full doses of warfarin, clots can be prevented with lower doses, about half of what is normally used to treat someone with a clot. The lower doses provide a safe middle ground, reducing the risk of more clots without increasing the risk of hemorrhage. That certainly sounds wonderful. Warfarin has been around for over fifty-years, so it’s available in a safe and effective generic version, although in 1998 only 18% of users chose the generic. It was first discovered in the 1930’s when researchers investigated the cause of hemorrhagic illnesses in free-ranging cattle. What they found was a substance called coumarin that’s present in the stems of sweet clover. Coumarin gave rise to warfarin which is the active ingredient in most rat and mouse poisons, and in more refined form, available for human therapy under the brand name Coumadin. Warfarin has its drawbacks. Not only does it increase the risk of bleeding by inhibiting blood clotting, but its metabolism is easily influenced by outside factors, so that the amount of clotting inhibition that occurs at any given dose can fluctuate depending on what other substances a person has ingested - both in terms of other drugs and in terms of food. It’s so easily influenced, in fact, that someone’s written a Coumadin cookbook to help patients prepare meals that won’t interfere with their Coumadin therapy. This means that the drug requires very close monitoring to be used safely. When everything is stable, that usually translates into once a month blood tests to insure that the anticoagulation effect is within the therapeutic range - neither too high, nor too low. But, if a dosage change is required, or if a new medication is introduced, then that testing becomes more frequent, usually within a week or a few days of starting the medication. That can mean a major life-style hassle for the patient, as well as an expense. Most of my warfarin patients complain bitterly about being on it. And that’s what bothers me about this study. It only tracks the risk of taking warfarin over a mean of two years The trial was terminated early after 508 patients had undergone randomization and had been followed for up to 4.3 years (mean, 2.1). We don’t know how that risk pans out after ten, fifteen, or thirty years of warfarin therapy. That’s something that we should keep in mind before rushing to put everyone on it for life. But that doesn’t stem author Dr. Paul Ridker’s (of C-Reactive Protein fame) enthusiasm: "This really ought to change the standard of care overnight," said Dr. Paul Ridker, the first author of the study and director of the center for cardiovascular disease prevention at Brigham and Women's Hospital in Boston. But, as the accompanying editorial points out, not only is warfarin tricky to use, there is some conflicting data out there that isn’t getting quite the publicity that this piece is (In fact, I couldn’t locate a link to the article the editorial mentions): However,Kearon et al.have simultaneously reported in preliminary form the results of a different randomized,double-blind trial of similar size that found that low-intensity warfarin (INR,1.5 to 1.9 )was significantly less effective than conventional-intensity warfarin (INR,2.0 to 3.0)for extended prevention of recurrent venous thromboembolism, without significant differences in the rate of bleeding complications. It is difficult to reconcile these findings and to make definitive recommendations regarding the optimal intensity of anticoagulation therapy for long-term secondary prevention without data from a risk –benefit analysis in a three-way comparison of conventional-intensity,low-intensity,and no anticoagulation therapy following at least three months of conventional-intensity warfarin therapy for an initial episode of venous thromboembolism. In other words, curb your enthusiasm. posted by Sydney on 2/26/2003 08:44:00 AM 0 comments 0 Comments: |
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