September 8, 2005

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In This Issue . . .

Predicting Adverse Events after Coronary Intervention: A New Role for an Old Standby?
Julie L McDowell


When cardiologists thread a catheter into a patient’s arteries, or perform any other percutaneous coronary intervention (PCI) on a patient, they are reducing blood flow to the heart—putting the patient at risk for adverse outcomes such as increased heart damage or even death. Some studies suggest that levels of the cardiac enzyme creatine kinase myocardial band (CK-MB) can be predictive of poor outcomes, but there is considerable debate over what cutpoints are appropriate. This month’s Strategies looks at some recent dialogue on the CK-MB debate, and what laboratory directors need to know about this enzyme’s clinical utility for such procedures.

Adverse outcomes or periprocedural myonecrosis (PM), including heart damage and death, following PCIs are not uncommon, and are frequently accompanied by an increase in CK-MB to > 3 times the upper limit of normal (ULN), according to an article by The Cleveland Clinic Department of Cardiology’s Deepak L. Bhatt, MD, and Eric J. Topol, MD, in the Aug. 9th issue of Circulation.

CK-MB is a continuous rather than a discrete variable, explained Bhatt. While appropriate cutpoints vary by study, levels three to fivefold greater than ULN likely indicate a PM. “Clearly a large CK-MB elevation, like greater than ten times the upper limit of normal, either with or without symptoms would carry some prognostic information for the patient. Somewhere between that—three, five, or ten times the upper limit of normal—is a gray zone where there’s some controversy over what is clinically important,” said Bhatt.

This variability factor prompted another leading cardiologist to express concerns about CK-MB’s role in predicting adverse outcomes based on some earlier data. “One of the problems with previous studies is that they were not only limited to successful procedures where the angioplasty or the stent procedure was the only new variable,” said Donald E. Cutlip, MD, Interventional Cardiology Section, Beth Israel Deaconess Medical Center in Boston, and co-author of another article on CK-MB in the same issue of Circulation. “Some of these data sets included patients who were coming into the hospital possibly with a heart attack in progress, so that the CK-MB elevation after the procedure may have actually been related to a spontaneous heart attack rather than something related to the procedure.” Another problem, he added, is that it is not possible to randomize patients by CK-MB levels, making it difficult to ascertain whether or not elevated levels are more likely to be obtained in patients who have had other issues, including a complication in the catheterization lab or complaining of chest pains after the procedure. “Since it’s not obtained on every patient, the comparisons may become biased,” Cutlip stated.

However, CK-MB is an important test for patients to have, even though it shouldn’t be viewed as an independent predictor of adverse outcomes, because it can help monitor post-procedure care, according to Cutlip.

Better Suited for the Research World?

Given the debate on cutpoints, the true value of CK-MB assessment could be in the research and development sector. For example, the marker may be most useful for evaluating new cardiac drugs and embolic protection devices (EPDs), which are commanding a lot of attention in the therapeutics and intervention world, explained Robert Christenson, Professor of Pathology, Medical and Research Technology at the University of Maryland School of Medicine in Baltimore. EPDs work to prevent thrombi from showering downstream in the heart’s vasculature where it can cause a blockage and myocardial infarction. The data gathered by Bhatt and Topol indicate that CK-MB could be used as a surrogate endpoint for trials for new devices, said Christenson. “That would be a lot cheaper and a lot faster, and a way that biomarkers could really contribute to healthcare and getting devices that could benefit patients on the market quicker and cheaper,” he added.

Bhatt agrees with Christenson that the data on CK-MB is most relevant in terms of evaluating novel drugs and devices. By setting a lower threshold to detect PM, it increases the ability of researchers to detect meaningful differences between potential drugs and devices.

“For clinical purposes, in a patient that is asymptomatic after what appears to have been a successful intervention procedure, I don’t think right now there is much utility in measuring CK-MB,” said Bhatt. “On the other hand, if one is doing research comparing one anticoagulant against another, I think it’s of great utility because there is definitely a correlation between CK-MB elevation and clinical events. If the endpoint is CK-MB elevation greater than three times of the upper limit of normal, within a reasonable number of patients, you might be able to discern a subtle difference or benefit of one drug or device versus another.”

For more information:
The Circulation article (2005;112:906-915) can be found online at
www.circ.ahajournals.org/cgi/content/full/112/6/906. Subscription is required, but reprints are available for a fee.

Reader Follow-up:

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