DURHAM, N.C. -- New findings from an international clinical trial led by Duke University Medical Center show that a low-cost diagnostic test routinely taken on patients with a suspected heart attack is a more sensitive marker of heart damage than many physicians realize.
A study published in the Jan. 19 issue of the Journal of the American Medical Association shows that even tiny increases in the test enzyme, known as creatine kinase-myocardial band, or CK-MB, can indicate injury to the heart and predict which patients with a suspected heart attack are at increased risk of death.
The enzyme is released into the bloodstream by dying heart muscle, and physicians have traditionally looked for substantial increases in CK-MB to help diagnose a heart attack. But this study is the first to definitively link even small levels of CK-MB elevation with increased risk of death and other negative outcomes, Duke researchers said.
"Physicians often ignore small increases in CK-MB, believing that only moderate to large increases signal a heart attack. But based on this study, physicians should pay attention to even the smallest increase," said the primary author of the study, Duke cardiologist Dr. John H. Alexander.
In addition to increased risk of death, patients with even slightly higher CK-MB levels also had higher rates of stroke, shock, congestive heart failure, ventricular arrhythmia, coronary procedures and bleeding complications, Alexander said. "The study also demonstrates that not all heart attacks are the same. The size of the heart attack matters and smaller is better."
The findings came from a double-blind, randomized, placebo-controlled trial of 9,461 patients at 726 hospitals in 28 countries. That study, known as PURSUIT (Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy), was designed to test the glycoprotein IIb/IIIa inhibitor eptifibatide (Integrilin), which is an intravenous "super aspirin."
Eptifibatide works by preventing platelets circulating in the blood from clumping together and forming a clot at the site of atherosclerotic plaque. Results of the trial, which was funded by Cor Therapeutics Inc. and published in 1998 in the New England Journal of Medicine, showed that treatment with eptifibatide was associated with reduced rates of death or heart attack by 30 days in these patients.
As part of the study, three CK-MB samples were collected from each patient at eight-hour intervals after enrollment into the trial. Researchers from the Duke Clinical Research Institute have now gone back and analyzed CK-MB data from these patients, along with their mortality rates at 30 days and six months after hospital admission, to determine the relationship between elevated CK-MB and risk of death.
They found that statistical analysis confirmed a strong relationship between CK-MB and mortality risk, even after adjustment for other baseline factors:
- In patients with normal peak CK-MB levels, the mortality rates were 1.8 percent and 4.0 perecnt at 30 days and six months, respectively.
- In patients with CK-MB elevated up to twice normal levels, those rates were 3.3 percent and 6.2 percent.
- For those with CK-MB levels 3 to 5 times normal, mortality rates were 5.1 percent and 7.5 percent.
- And for patients whose CK-MB was more than 10 times normal, mortality rates rose as high as 8.3 percent at 30 days and 11.0 percent at six months.
"This study extends the observations made in angioplasty trials that myocardial necrosis at even minimal levels above normal is important, raising the possibility that lowering the risk of myocardial necrosis through novel therapies could translate into a mortality benefit for patients," said Duke cardiologist Dr. Robert A. Harrington, senior author of the study. Still, the authors caution that further study is needed. "The long-term clinical impact of reducing the size of infarctions still needs to be confirmed in other studies," Alexander said.
Journal
JAMA