WASHINGTON – A trio of experimental drugs has doctors hopeful that for the first time in decades, millions of people at risk of lethal blood clots may soon get easier treatment.
The first goal is a pill option for people who now need daily blood-thinning shots for weeks after knee or hip replacement surgery.
But the ultimate goal is an alternative to that old standby warfarin, also called Coumadin, the nation's most troublesome lifesaver because of side effects and restrictions its 2 million users face.
Now in late-stage testing in thousands of Americans are three pills that work to prevent blood clots in ways that promise to be less burdensome. One of the trio, Boehringer Ingelheim's Pradaxa, just began selling in Europe.
The drug research comes as Medicare is considering withholding payment from hospitals when at-risk patients develop clots in their veins, usually the legs – a common preventable cause of hospital deaths. The National Quality Forum has estimated that only about a third of patients who need protective blood thinners while hospitalized get them.
Known medically as a “deep vein thrombosis” or DVT, such a clot can kill quickly if it moves up to the lungs. There aren't good counts, but recent estimates suggest that about 900,000 people a year suffer a vein clot, and nearly 300,000 die. Being immobile for long periods, such as during hospitalizations or even long airplane flights, can trigger a clot. Vice President Cheney suffered one after a long trip last year. NBC correspondent David Bloom died of one in 2003 after spending days in a cramped military vehicle while covering the invasion of Iraq.
But there are a variety of risks, including increasing age, smoking, birth control pills, obesity – and especially, big surgeries like knee or hip replacements.
Doctors use faster-acting shots of the blood thinner enoxaparin to protect orthopedic surgery patients. But warfarin is a top treatment once a vein clot strikes – and the leading protection for other types of clots, such as strokes caused by the irregular heartbeat atrial fibrillation. But too many of those patients go unprotected, too, because warfarin is so hard to use. Dangerous bleeding is the worst side effect, but it requires monthly blood checks because diet and other factors can throw off the dose.
“The need is substantial” for an easier alternative, says Dr. Richard Becker, a hematology and cardiovascular specialist at Duke University Medical Center who is monitoring the pipeline. “I don't know of a drug that has the inherent complexities and potential for harm that Coumadin does.”
Hopes have been dashed before. Just a few years ago, the highly anticipated blood thinner Exantra was pulled off Europe's market, and rejected here, because of surprising liver damage. So while trial results have U.S. specialists optimistic about the three new attempts, they're watching closely for any hints of problems.
“There are some huge benefits to these drugs, all three of them – if they play out,” says pharmacist John Fanikos of Boston's Brigham and Women's Hospital and the North American Thrombosis Forum.
In the pipeline:
Rivaroxaban tamps down action of a key player in blood clotting, called Factor Xa. Last month, the New England Journal of Medicine published two studies of more than 7,000 knee and hip replacement recipients who received either a daily rivaroxaban pill or today's standard injections. Pill users were less likely to suffer fatal and nonfatal vein clots. Bleeding and other side effects were similar with both drugs.
Johnson & Johnson, which is developing rivaroxaban with Bayer Healthcare AG, plans to seek Food and Drug Administration approval later this summer.
Pradaxa, or dabigatran, interferes with another blood clotting agent, called thrombin. European regulators cited research showing Pradaxa was as effective as standard shots in protecting orthopedic patients. Duke's Becker cautions that one U.S. study didn't show as big an effect; other research is continuing. This drug works similarly to the ill-fated Exantra, but Becker says there are no signs of liver toxicity so far.
Bristol-Myers Squibb's apixaban works against the same clotting factor as rivaroxaban; its key studies are under way.
Orthopedic surgery is an easier hurdle – because vein clots are quick and common – than proving if these pills will work as well as warfarin for people who need longer-term care. Stay tuned: Large studies comparing warfarin to each have begun at hospitals nationwide.
If they work, their targeted action promises fewer side effects, dietary restrictions or dose problems than warfarin, Fanikos notes. But warfarin still will play an important role, he cautions – since the generic form sells for as little as $40 for a three-month supply.
EDITOR's NOTE – Lauran Neergaard covers health and medical issues for The Associated Press in Washington.
To find enrolling studies: www.clinicaltrials.gov
