Small doses of an old-fashioned blood thinner can safely and sharply cut the risk that people who have survived life-threatening blood clots will suffer a recurrence, according to a major new study.
Steady low levels of the drug warfarin can reduce by 64 percent the risk for new clots, which hit an estimated 750,000 Americans each year, the study found.
The results were so striking that the National Institutes of Health stopped the federally funded study prematurely because officials decided it would be unethical to continue giving half the participants a useless placebo. Because the findings could immediately save lives, the New England Journal of Medicine released the results of the study yesterday even though they are not scheduled to be published until April.
"This is a win-win for everyone involved," said Paul M. Ridker, a professor at Harvard Medical School in Boston, who led the study. "Now we have a very safe, very effective, very inexpensive long-term method of preventing recurrent blood clots. This should change the standard of care overnight."
Clots form for a variety of reasons. Some people are genetically predisposed to them. Others get them when they sit still for too long, such as during long airplane trips. The clots can be extremely painful, and life-threatening if they get into the lungs.
About 25 percent of people who have had a clot will develop another one. People who get a clot are typically given a blood thinner for three to six months to minimize the chances of recurrence. But long-term use of blood thinners is considered dangerous because it can increase the risk for potentially life-threatening bleeding.
The National Institutes of Health funded the new study, the first of its kind, to find out whether it was safe and effective to give people warfarin for long periods at very low doses after they have suffered clots, known as deep vein thrombosis when they occur in a leg and pulmonary emboli when they occur in a lung. Warfarin, also known as Coumadin, is a well-known blood thinner that has been used for decades.
Researchers had planned to study 750 people for seven years, giving half the patients about half the dose of warfarin usually used and the remaining subjects a placebo. But the study was terminated Dec. 4 after only 508 patients were enrolled at 52 sites in the United States, Canada and Switzerland. They were followed for an average of only two years because the protective effect was shown to be so dramatic and safe.
Of the 253 patients who received a placebo, 37 suffered another clot, compared with 14 of the 255 patients who received warfarin. The low dose of warfarin did not boost the risk for bleeding.
"These results suggest that low-dose warfarin is a safe and effective way to prevent future episodes of these potentially serious blood clotting problems," said Claude Lenfant, director of the National Heart, Lung and Blood Institute.
Based on the findings, "it is reasonable for clinicians to adopt, at least for now, this regimen of secondary prophylaxis against venous thromboembolism for patients who require more than three months of anticoagulation therapy after an initial event," wrote Andrew I. Schafer of the University of Pennsylvania School of Medicine in Philadelphia in an article that will accompany the study in the medical journal.
Schafer noted, however, that a similar study recently found the treatment to be less effective. "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," he wrote.
But Ridker said his findings were so strong that there was little doubt the treatment was safe and effective. His main concern was that, because warfarin is no longer under patent, pharmaceutical companies have no incentive to promote the drug's use.
"This is a project that no pharmaceutical company would have undertaken," Ridker said.
Drug companies are, however, investigating whether newer blood thinners may be equally safe and effective but possibly easier to administer.
Stephan Moll of the University of North Carolina at Chapel Hill, who helped conduct the warfarin study, said he was also involved in another project evaluating a new blood thinner called Exanta.