Extra caution needed in selecting heart attack patients for use of clot-busing

November 13, 2001

ANAHEIM, CA. - While clot-busting drugs known as thrombolytics have shown great effectiveness in treating heart attack patients in hospital emergency rooms, a new Duke University Medical Center analysis provides additional evidence that great care must be taken in deciding which patients should receive this life-saving therapy. Many patients brought to emergency rooms with symptoms of heart attacks are given thrombolytic drugs to open blocked arteries and keep the heart from being starved of oxygen-rich blood. Nearly 1 percent of the patients, however, suffer from potentially lethal bleeding in the brain known as intracranial hemorrhage (ICH).

The Duke researchers looked at data collected in a recent large multi-center trial and found that 2 percent of the patients treated with thrombolytics were later found to be inappropriate candidates and, furthermore, that these patients had significantly worse outcomes than the other 98 percent. While this finding was not unexpected, the researchers say the results provide a cautionary note to physicians practicing in the community who may not follow the same strict screening protocols used when enrolling patients in formal clinical trials. Cardiologist Dr. John Alexander of the Duke Clinical Research Institute (DCRI) prepared the results of the Duke analysis for presentation during the 74th annual scientific sessions of the American Heart Association in Anaheim, Calif. "For physicians, the risk of ICH is the No. 1 limiting factor in the use of thrombolytic drugs," Alexander said. "If 2 percent of patients in the very controlled setting of a clinical trial were getting a drug that they shouldn't, it is highly likely that a higher percentage of patients are getting thrombolytics inappropriately in the real world of clinical practice.

"While we don't want to alarm people unnecessarily, the results of this study should make doctors pay extra attention before using these drugs," he said. In his analysis, Alexander looked at the data collected during a 16,949-patient trial known as ASSENT-2 that compared the effectiveness of two different thrombolytic agents - t-PA or TNK, a genetically altered version of t-PA. Alexander found that 324 patients (2 percent) received thrombolytics but were later found to have medical conditions that should have ruled them out.

These patients with medical contraindications were three times more likely to die 30 days after treatment (15.3 percent vs. 5.7 percent) and were more than eight times as likely (6.7 percent vs. 0.8 percent) to have an episode of ICH. There was no difference in adverse outcomes between the two different thrombolytics.

"When a patient comes to the emergency room with symptoms of a heart attack, doctors must act quickly in deciding whether or not to treat the patient with thrombolytics," Alexander said. "On average, if thrombolytics were used in the trial, they were started within 40 minutes of arrival in the emergency room."

The challenge facing these doctors, Alexander explained, is that it can be difficult to determine if a patient should be excluded within the short period of time necessary for the thrombolytic therapy to be effective. The five major criteria that would exclude enrollment were: a history of stroke or transient ischemic attack (TIA), 175 patients; hypertension, 65 patients; any minor head trauma, 39 patients; current use of anti-coagulation therapy (coumadin), 35 patients; or damage to central nervous system, 27 patients. While all of these criteria increase the risk of a bleeding episode, it is not always possible in the fast-moving environment of an emergency room to be absolutely certain that a patient doesn't have one or more of these factors, Alexander said. "It can be challenging in the emergency room to get a complete medical history, but the bottom line is that the utmost care must be taken in trying to find out as much about these patients as possible," Alexander said.

Dr. Cecelia Bahit, until recently a cardiology fellow at the DCRI, played an important role in the DCRI analysis.

Genentech, South San Francisco, Calif., and Boehringer Ingelheim, Germany, funded the original ASSENT-2 trial. Alexander's team analysis of the ASSENT-2 data was supported by the DCRI.
Note to editors: Dr. John Alexander can be reached at (919) 668-8955 or by e-mail at alexa017@mc.duke.edu. A photograph of Dr. Alexander is available at http://dukemednews.duke.edu/gallery/detail.php?id=474.

Duke University Medical Center

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