Tailored Use of Platelet Inhibitors may Prevent Second Heart Attacks
ANAHEIM, CA -- Researchers at Duke University Medical Center think they know why glycoprotein IIb/IIIa platelet inhibitor drugs, collectively known as "super aspirins," produce only modest benefit for patients with acute coronary syndromes -- they are often being used on patients who gain very little benefit.
In the process of tabulating results on a trial of lamifiban, one of three intravenous super aspirins that have been tested, the researchers discovered that a simple blood test identified patients who benefited markedly when the drug was used. In those patients, improvement in the risk of death and a second heart attack was about 50 percent, compared to patients who received a placebo.
In contrast, overall data on all patients in the lamifiban trial shows only a modest, statistically insignificant improvement, a similar improvement to that seen in tests of eptifibatide and tirofiban, two other intravenous-use GP IIb/IIIa receptor inhibitors already on the market
"This is good news. It shows us that we can potentially refine the use of IIb/IIIa inhibitors and direct them to the patients who can really benefit from them," said the study's lead investigator, Dr. Robert Harrington of the Duke Clinical Research Institute. He prepared his findings for presentation at a press conference held Tuesday at the annual scientific session of the American College of Cardiology. The research was funded by Hoffman-LaRoche, Inc., developers of lamifiban.
Harrington said that use of the super aspirins in the United States is tepid - only about 15 percent of eligible patients are put on them. "But with this new information, we may have the ability to target the power of these drugs," he said.
The three super aspirins are all cousins of each other in that they attempt to prevent platelets circulating in the blood from clumping together and forming a clot at the site of atherosclerotic plaque. These drugs are delivered intravenously over a three-day period to patients who suffer from unstable angina or are at risk for a second heart attack. (They are not used on patients who are receiving thrombolytic therapy to break up existing blood clots.) Oral forms of these super aspirins have not shown any benefit over aspirin use.
The clinical trial in which the Duke Clinical Research Institute tested lamifiban was known as PARAGON B. It enrolled 5,225 patients in 29 countries and gave them either a dose of lamifiban that was tailored to their weight, gender and kidney function, or a placebo, or dummy, drug. All patients also received aspirin and heparin.
Results show that at the end of 30 days, 11.8 percent of patients treated with lamifiban had either a second heart attack, recurrent ischemia, or died, compared to 12.8 percent of patients treated with a placebo. "This is a lukewarm response," Harrington notes.
The research team then conducted a sub-study to look at which patients were most at risk, and obtained blood samples for further analysis. As part of the analysis, researchers looked at the level in patients' blood of a protein known as "troponin T," which is a marker of dying muscle tissue. It is a regulatory protein that helps heart muscle contract and once this muscle starts dying, cell membranes break down and internal cellular material, including proteins, is released and carried away by blood. A test that measures troponin levels is available, and previous studies have indicated that 25 percent to 40 percent of typical unstable angina patients test positive when they are admitted into the hospital, Harrington said.
Of the patients in this study who had a positive troponin level at admission, 11 percent had an adverse event within 30 days when treated with lamifiban, compared to 19.4 percent of patients treated with a placebo. That's a 49 percent reduction in the risk of adverse events, Harrington said.