A study estimates about 1,500 U.S. heart attack victims may die needlessly each year because they receive the wrong doses of clot-dissolving drugs. While the medicines are clearly life-saving if given properly, the new work shows they can also prove fatal when nurses fail to administer the precisely correct dose at the right time - a mix-up that apparently happens frequently in hectic emergency rooms.

These drugs - TPA, streptokinase and Retavase - are standard treatment for patients who arrive at the emergency room within six hours of the start of symptoms. Last year, the medicines were given to about 260,000 heart attack patients in the United States. Given quickly, the drugs can clear away the blood clots that cause heart attacks before permanent damage results. Emergency room teams typically try to get the treatment started within a half-hour of the patient's arrival.

Researchers from Brigham and Women's Hospital in Boston reviewed the results of eight large studies involving almost 50,000 patients to see how commonly errors occur. They found that TPA, the most complicated of the three drugs to give, results in the most error

Every place the investigators looked, the simpler the dosing, the fewer the errors they found. And if they had an error, it was bad news. The number of TPA errors varied from study to study, ranging from 12 percent to 16 percent of patients treated. Errors occurred in 8 percent to 11 percent of patients getting streptokinase and in about 5 percent of those receiving Retavase, the simplest of the drugs to administer.

The death rate was 7 percent to 8 percent if the drugs were given properly and double that if mistakes were made. The investigator estimated that 22,500 patients nationally get the wrong dose of clot-dissolving drugs annually, and this error results in approximately 1,500 deaths.

This therapy has to be given within minutes, so you have to rush. So there is a big push. It's a setting where you could imagine errors happening. In a busy emergency department, staff members may get distracted by even sicker patients who need immediate attention.

TPA - tissue plasminogen activator or Activase - was the first widely used clot dissolver but is the hardest to give. Patients must receive two separate infusions, the first for 30 minutes and the second for 60 minutes. Also, those who weigh less than 150 pounds must get a lower dose, depending on their weight.

Typical mistakes include giving the drugs too fast or too slowly, forgetting to give the second infusion on time and giving too high or low a dose. The analysis suggests that any of these errors can increase the death rate. Errors were more common in women than in men, mostly because women are more likely to need less than the standard dose because of their size.

TPA is given according to a fairly rigid cookbook of timing. It's a high-wire act. Small screw-ups in timing can have important consequences. Retavase results in the fewest errors because it is given in two simple injections a half-hour apart, not timed infusions. Awaiting approval by the Food and Drug Administration is an even simpler drug, a new form of TPA called TNK or tenecteplase, that will be given as a single injection.

Annual meeting of the American College of Cardiology in Anaheim, California Mach 11, 2000