New Synthetic Drug Cuts Clot Risk

Reduces deep vein thromboses in joint replacement patients

THURSDAY, May 16, 2002 (HealthDayNews) -- A new-generation blood thinner significantly cuts the risk of blood clots in the legs of patients having major joint surgery.

The drug, fondaparinux sodium, reduced the odds of the potentially life-threatening deep venous thromboses (DVT) by roughly 50 percent over a conventional blood thinner, say two new studies and two previously published reports.

However, the synthetic compound, sold jointly by the European drug makers Sanofi-Synthelabo and Organon under the brand name Arixtra, carries a much higher risk of serious bleeding complications than the other medication, say Swiss researchers who analyzed the trial data. Since most DVTs are ultimately harmless, experts say the higher risk of threatening bleeds might discourage some doctors from prescribing the new medication.

The two studies and the Swiss commentary appear in the May 18 issue of The Lancet.

Dr. Alexander Turpie, a clot expert at McMaster University in Ontario and a co-author of the two studies, says he didn't believe the heightened bleeding risk -- which he minimized -- would discourage doctors from prescribing the new drug. "The benefit-to-risk ratio is enormously in favor of the drug," he says.

Heparin and its cousins are quite effective, Turpie says, and it's difficult for a newcomer to improve on an effective medication. "That's what this drug clearly shows," he says.

Blood clots in the legs are a common complication of joint surgery, the result of immobility, thickened blood and damage to the leg vessels. The blockages occur in between 16 percent and 30 percent of all hip replacement operations, even when blood thinners are used, and in up to 60 percent of patients who don't get the drugs.

If the clots reach the lungs they can be lethal, though less than .5 percent of hip surgery patients die from DVT.

Those same blockages are implicated in "economy-class syndrome" and other clots linked to long-haul travel.

Arixtra was approved by the U.S. Food and Drug Administration last December. The injected medication muzzles Factor Xa, a key molecule in the clotting process.

The latest studies -- which included researchers from Europe, Canada and the United States -- compared Arixtra with a blood thinner called enoxaparin, a cousin of heparin. One trial included about 2,300 men and women receiving hip replacements; the second had 2,275. The two previous trials compared the two drugs in other joint surgeries, including hip fracture repair and knee replacements.

Two Swiss scientists combined the results from the two new trials with the two previous studies. They found that, on average, Arixtra reduced the risk of DVT by 55 percent, compared with enoxaparin. It also cut the number of proximal thromboses -- a less common but similar form of clotting -- by 55 percent.

However, the incidence of major bleeding episodes was higher, too -- 11 times more likely in those receiving artificial knees. When the four trials were pooled, patients on Arixtra were 54 percent more likely than those on the more conventional blood thinner to bleed dangerously (2.7 percent versus 1.7 percent overall). No case of fatal bleeding occurred in either of the two new trials.

Wim Mol, general manager for the Organon-Sanofi-Synthelabo partnership's West Orange, N.J. office, disputed the analysis of Arixtra's bleeding risk.

Only the study conducted in knee replacement patients showed a significant difference between the new drug and heparin, Mol says. Yet in that trial, many of the patients were put on the compound too early after surgery.

Mol called his company's product "a very important advance" that offers previously "unseen reductions in DVT."

Arixtra costs about $30 a day, $5 more than heparin therapy. The drug is taken for roughly 10 days, starting six to eight hours after treatment.

What To Do: For more on Arixtra, try the U.S. Food and Drug Administration. To learn more about deep vein thrombosis, visit HealthCentral.

SOURCES: Alexander Turpie, M.D., professor, medicine, McMaster University, Hamilton, Ontario; Wim Mol, Ph.D., general manager, Organon-Sanofi-Synthelabo, West Orange, N.J.; May 18, 2002, The Lancet
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