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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.