Abciximab enhances angio, may prevent procedure
Abciximab enhances angio, may prevent procedure
Super-aspirin gives a kick to clot-buster
The monoclonal antibody abciximab (Centocor’s ReoPro) has been in the research literature of late, both for its ability to prevent heart attack in some high-risk patients undergoing angioplasties and for its capacity to spare patients from that procedure or from coronary artery bypass graft (CABG) surgeries. Two teams of investigators, working separately, presented their work in recent issues of two medical journals.
One team of researchers reported that administering abciximab before and after angioplasties can benefit patients.1 High-risk unstable angina patients ready to undergo angioplasty to restore blood flow to an obstructed artery often have high levels of serum troponin T (TnT), a marker for heart muscle damage. (See Cost Management in Cardiac Care, April 1998, pp. 41-46.) Levels increase substantially within several hours after an unstable angina attack, peaking at 10 to 24 hours.
A recent study included only patients with serious unstable angina — having at least one obstructed heart artery that could be effectively treated with angioplasty — and high levels of TnT. Researchers looked at blood samples of 890 patients who were assigned to one of two treatment groups: Patients who received an injection of abciximab — also called super-aspirin — 18 to 24 hours before angioplasty plus continuous infusion of abciximab into the vein until one hour after angioplasty; or patients who received a matching pre-angioplasty injection and infusion of a placebo during angioplasty.
Six months after angioplasty, among the individuals in the group who received abciximab, 9.5% had heart attacks or deaths, compared to 23.9% of the people in the placebo group.
The researchers concluded that patients with high levels of TnT are most likely to benefit from abciximab in combination with angioplasty. "This study is important because it raises the possibility that even after unstable angina occurs and the bells go off, heart attack can be prevented with medical therapy," states Richard Pasternak, MD, American Heart Association spokesman and director of preventive cardiology at the Massachusetts General Hospital in Boston.
Combo is more effective than either alone
A second team of investigators reported that the combination of alteplase (Genentech’s t-PA or Activase) and abciximab could spare patients from angioplasty or CABG surgery.2
Elliott M. Antman, MD, of Brigham and Women’s Hospital in Boston, and a team tested 888 heart attack patients and compared the ability of different amounts of the two drugs, singly or in combination, to dissolve blood clots and improve blood flow at 60 and 90 minutes after injection. A combination of half the standard dose of alteplase and a standard amount of abciximab improved blood flow in 72% of patients at 60 minutes and in 77% at 90 minutes. Alteplase alone eased flow in 43% of patients at 60 minutes, and in 62% at 90 minutes. Alteplase costs about $2,000 for a standard dose; abciximab, about half of that. The short-term savings even out, but with the combination of therapy may save money in the long run if it reduces the need for angioplasty and CABG.
Abciximab weakens the clot’s structure
The two drugs attack clots in different ways. Abciximab and other drugs in the class of so-called glycoprotein IIb/IIIa antagonists weaken the structure of the clot by breaking up platelet clumps, allowing alteplase to penetrate more deeply into the clot. Abciximab is used in angioplasty and for unstable angina, but does not have broad approval for use against myocardial infarction. Nevertheless, doctors are now expected to use the combination for heart attacks.
Antman told The New York Times that he and his team got the idea for the combination therapy three years ago after piecing together clues from animal research and clinical trials in which patients happened to receive both drugs.3
Another trial, Gusto IV, will begin next year to compare survival rates between patients treated only with the standard dose of retaplase, or r-PA (Centocor’s Retavase) and those receiving a combination of the standard dose of abciximab and a reduced retaplase dose. Preliminary data from a small earlier combination trial of the two drugs were encouraging, with 77% of patients achieving optimal blood flow after receiving the regular dose of abciximab and three-fourths of the retaplase standard dose. Retaplase is given by simple injection, unlike the super-aspirins, which require IV infusions and are always given in hospitals. Because of retaplase’s ease of administration, a study has been launched to test the effectiveness and safety of giving heart attack patients the drug in the ambulance before they reach the hospital. (See CMC, January 1998, pp. 4-6, for a set of articles on equipping an ambulance with a 12-lead EKG and a retaplase setup.) The goal is to find out if people receiving the fast treatment fare better or live longer than those who have to wait the 20 minutes or longer it often takes ambulances to reach the hospital.
References
1. Hamm CW, Heeschen C, Goldmann B, et al. Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels. N Engl J Med 1999; 340:1,623-1,629.
2. Antman EM, Giugliano RP, Gibson CM, et al. Abciximab facilitates the rate and extent of thrombolysis: Results of the thrombolysis in myocardial infarction (TIMI) 14 trial. Circulation 1999; 99:2,720-2,732.
3. Altman LK. Ganging up on blood clots with a new drug cocktail. The New York Times, June 1, 1999:F2.
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