New drugs could simplify clot prevention

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, a troubling lifesaver due to side effects and restrictions for its two million users.

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 are not 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.

Risks for getting a clot include increasing age, smoking, birth control pills, obesity - and big surgeries such as 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 from other types of clots. Dangerous bleeding is the worst side effect of warfarin, but it requires monthly blood checks because diet and other factors can throw off the dose.

Hopes have been dashed before. Just a few years ago, the blood thinner Exantra was pulled off Europe's market, and rejected here, because of liver damage. So while trial results have U.S. specialists optimistic about the three new attempts, they are watching 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.

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 federal 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. But one U.S. study didn't show as big an effect. This drug works similarly to the ill-fated Exantra, but there appear to be no signs of liver toxicity so far.

Bristol-Myers Squibb's apixaban works on the same clotting factor as rivaroxaban; key studies are ongoing.

If they work, their targeted action promises fewer side effects, food restrictions or dose problems than warfarin, Fanikos notes. But warfarin will remain important, he said, since the generic form sells for as low as $40 for a three-month supply.