Trial Looks at Timing of Anti-Clotting Drugs for Heart Attack Patients

Findings lean toward using them later, not sooner

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TUESDAY, Feb. 13, 2007 (HealthDay News) -- Drugs used in emergency rooms to reduce heart patients' clotting risks can also boost their odds for dangerous bleeding, a new study shows.

The major trial, involving more than 9,200 people treated in 17 countries, found that doctors may want to hold off giving these drugs -- called glycoprotein IIb/IIIa inhibitors -- to patients until just before they undergo angioplasty, to help lower bleeding risks.

"There were a lot of folks who were on the fence on this, who didn't know what the best way to treat patients was," said the study's lead author, Dr. Gregg Stone, a professor of medicine at Columbia University College of Physicians and Surgeons, in New York City. "They might prefer not to start them upfront [on the drugs], because it means another IV, extra cost, and extra bleeding risk -- but they didn't know if it was safe not to. So, these results are going to be very reassuring."

Still, the findings, published in the Feb. 14 issue of the Journal of the American Medical Association, don't come down solidly on giving glycoprotein IIb/IIIa inhibitors either early or late, and doctors may still want to make their decisions on a case-by-case basis, another expert said.

"Based on this data, I don't think it would fundamentally change how these drugs are used in acute coronary syndrome patients right now," said Dr. Kenneth Mahaffey, associate professor of medicine at Duke University Medical Center in Durham, N.C. He was not involved in the study, but co-authored a commentary on the research for the journal.

Acute coronary syndromes (ACS) include events such as sudden chest pain and even heart attack. Patients with ACS must be managed so that clots do not build up that could trigger an ischemic attack, such as a stroke or heart attack. These clots are especially problematic during invasive procedures such as angioplasty.

Most ACS patients already receive some type of blood-thinner, such as heparin, upon admission to a hospital. But glycoprotein IIb/IIIa inhibitors, which include abciximab or eptifibatide, can also help cut clotting risks.

"All of the guidelines do recommend the use of glycoprotein IIb/IIIa inhibitors routinely in a heparin-based regimen," Stone explained. "But the issue is, do you give them to all patients as soon as you see them in the emergency room, or do you wait and take them into the catheterization lab, and only use them in patients who are going to have an angioplasty?"

There is a good reason to consider delaying the use of glycoprotein IIb/IIIa inhibitors: They can boost bleeding risks. Bleeding can pose serious health dangers, especially in elderly patients.

To help settle the issue, Stone, in collaboration with researchers in the United States, Germany and New Zealand, compared one-year outcomes for 9,207 patients treated at 450 centers worldwide.

Patients with moderate- to high-risk ACS were treated with heparin and either abciximab or eptifibatide, with the major difference being that some received their glycoprotein IIb/IIIa inhibitor immediately, while others received it an average of five hours later.

"The main finding was that if you waited and didn't use these drugs up front, and just give them to people who need them during angioplasty, not only did you use much less of the agents -- from 97 percent down to 55 percent -- you also used them for a much shorter period of time and with much less bleeding," Stone said. Thirty-day rates of major bleeding dropped from 6.1 percent of patients in the group that got the anti-clotting drug soonest to 4.9 percent of patients who received it a few hours later.

But did putting off the use of these clot-inhibiting drugs boost ischemia risk?

Among patients in the "delayed-drug" group, Stone said, "There was a slight trend toward a very slight increase in adverse ischemic complications." Overall, 7.9 percent of patients in the delayed-drug group suffered an ischemic event in the month after their invasive treatment, compared to 7.1 percent of those who got the anti-clotting drug earlier.

"This difference did not reach statistical significance, however, and the only type of ischemic complication that tended to be increased was the most minor of all the types we measured," Stone noted.

So, based on the findings, "It seems like either strategy would be acceptable, but the one we would favor -- especially in elderly patients at an increased risk of bleeding -- would be to withhold the drugs from up-front use, waiting until you see what the angiogram shows, and then give the drug to those people who absolutely need it," Stone said.

Mahaffey was more ambivalent. He believes decisions as to when to use glycoprotein IIb/IIIa inhibitors still rely on the particulars of each patient.

"It's still a balance between waiting and having that slightly lower bleeding rate, or starting them earlier and having a slightly lower [heart attack] rate," he said.

Longer-term data from this and other trials, "may put us on the road to choosing one option or the other," Mahaffey said. "But I don't think that we will ever really have definitive evidence one way or the other from these data."

More information

Find out more about acute coronary syndromes at the American Heart Association.

SOURCES: Gregg Stone, M.D., professor, medicine, Columbia University College of Physicians and Surgeons, New York City; Kenneth Mahaffey, associate professor, medicine, Duke University Medical Center, Durham, N.C,; Feb. 14, 2007, Journal of the American Medical Association

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