New Drug No Substitute for Standard Blood-Clot Therapy
WEDNESDAY Sept. 12, 2007 -- Three studies on the new anti-clotting medication idraparinux found the drug was effective at treating deep vein thrombosis (DVT) and for the long-term prevention of blood clots. But it was not as effective as the usual treatment for potentially life-threatening pulmonary embolisms.
And, with long-term use, idraparinux appears to have a higher rate of serious bleeding complications than standard therapy.
"This wish to find new anti-coagulants (anti-clotting medications) is urgent," said lead researcher Dr. Harry Buller, chairman of the department of vascular medicine at the Academic Medical Center in Amsterdam, the Netherlands. "Our conclusion in the DVT study was that it was a good alternative. For pulmonary embolism, idraparinux was not as good as standard therapy."
And, Buller said, in the study that compared idraparinux to standard therapy for preventing the formation of new blood clots, the new drug was effective, but "there is a bleeding risk that is too high."
"Clearly, this drug in its present form won't come to the market," said Buller, who added that the drug's manufacturer, Sanofi-Aventis, is working on the medication and adding a biomarker to the drug so it could be quickly removed from the system if a complication such as excessive bleeding occured.
Sanofi-Aventis provided support for all three studies.
Buller said that in western societies, about two to four people per every 1,000 develop either a deep vein thrombosis or pulmonary embolism each year. That means that hundreds of thousands of people in the United States experience these problems each year, he said.
The current treatment regimen includes intravenously delivered or injections of the blood-thinner heparin, followed by six to 12 months of warfarin, an oral anti-coagulant. The currently available treatments are effective but necessitate careful monitoring and require patients to modify their diets and watch what medications they take to prevent complications.
"We wanted to find a medication that was a little safer, more patient-friendly and that could improve the quality of life," Buller said.
Two of the studies, published in the Sept. 13 issue of the New England Journal of Medicine, compared the use of idraparinux to standard therapy (heparin, followed by warfarin) for both DVT and pulmonary embolisms.
The DVT study included 2,904 people, and the pulmonary embolism study had 2,215 participants. In each group, the study volunteers were randomly chosen to receive either once-weekly injections of idraparinux or heparin, followed by three to six months of warfarin therapy.
The incidence of recurrence in the DVT group was 2.9 percent for those on idraparinux compared to 3.0 percent for those on standard therapy. In the pulmonary embolism group, the rates of recurrence were 3.4 percent in the idraparinux group versus just 1.6 percent in the usual treatment group.
Buller said that the frequency of recurrence in the standard therapy group was extremely low -- much lower than would normally be expected -- in the pulmonary embolism study.
"We've never seen this low frequency in studies. It's always around 3 to 4 percent," said Buller, who believes that this is likely a chance finding.
The third study, also published in the Sept. 13 New England Journal of Medicine, compared the use of idraparinux to a placebo in people who had already completed six months of treatment with either warfarin or idraparinux.
Just under half of the 1,215 people recruited for this study were randomly selected to receive six months of idraparinux, and the rest received a placebo. Just 1 percent in the idraparinux group had a recurrent blood clot, compared to almost 4 percent for those on a placebo. However, those who received an additional six months of idraparinux had a higher incidence of bleeding complications -- 3.1 percent versus 0.9 percent for those on a placebo.
"The long duration of action for idraparinux is a benefit, but it's also a hazard, because there's no antidote," said Dr. Edward L. Amorosi, a hematologist at the New York University Medical Center.
"It appears to be a more effective anti-thrombotic for DVT, but it's not safe enough to make it standard treatment," he added.
Buller said that Sanofi-Aventis is conducting research on pulmonary embolism treatment with a newer version of idraparinux, and that results should be available within a year. The new trial should help answer the question of whether or not the findings in the current pulmonary embolism trial were a statistical anomaly or not, he said.
To learn more about blood clots, visit the U.S. National Library of Medicine.
Posted: September 2007