Aggressive Heart Therapies Still Underused, Despite Blood Chemical Status
NEW ORLEANS -- Physicians are underutilizing aggressive therapies such as anti-clotting drugs and invasive procedures in heart patients, despite the presence of biochemical markers in the blood indicating heart muscle death, according to a new analysis by cardiologists at Duke University Medical Center.
The researchers studied patients who came to the emergency room with symptoms of a heart attack and how they were treated based on the results of two biochemicals in the blood -- creatine kinase-MB (CK-MB) and troponin. Both are proteins within cells that leak into the bloodstream as the cell wall breaks apart during cell death. The difference between the two is that troponin is only released by heart muscle, while CK-MB can be released by both dying heart and skeletal muscle.
In their analysis of a heart attack registry of almost 30,000 patients, the researchers found that 28.4 percent of the patients had differing, or discordant, marker results. Furthermore, the researchers found that when the two blood chemical results conflicted, the treatment strategy tended to be determined by the status of the CK-MB, an older and less specific test, and not by troponin, which can identify high-risk patients.
The results of the current analysis were presented today (March 10, 2004) by Duke cardiologist Kristin Newby, MD, at the annual scientific sessions of the American College of Cardiology.
"Patients who had positive troponin levels had increased mortality regardless of the CK-MB status, but CK-MB elevation in the absence of elevated troponin did not predict increased mortality," Newby said. "Paradoxically, the early use of newer anti-platelet drugs and invasive procedures among troponin-positive patients appears biased by CK-MB status despite this risk pattern."
Newby said that recognition of these risk differences may contribute to more appropriate use of antiplatlet therapy and angioplasty.
For their analysis, the researchers consulted the nationwide quality improvement initiative named CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC and American Heart Association Guidelines). The registry collects data on outcomes and usage of proven drugs like aspirin, beta-blockers, heparin and anti-platelet drugs such as glycoprotein (GP) IIb/IIIa inhibitors, as well as the use of catheterization and angioplasty procedures.
CRUSADE focuses on heart patients with unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI). These patients typically arrive at emergency rooms with chest pain, but often will not have telltale signs of a heart attack on the initial electrocardiogram. They might only be diagnosed with a heart attack when the results of the blood tests are reported a few hours later.
While patients with acute STEMI are at higher risk of dying within 30 days of their hospital stay, patients with UA/NSTEMI actually have a higher risk of dying six months and one year after initial hospital presentation. It is estimated that about 1.3 million Americans are hospitalized each year with UA/NSTEMI
CRUSADE continuously gathers data from more than 400 participating U.S. hospitals on treatments for patients with UA/NSTEMI and provides regular feedback to hospitals with the ultimate goal of improving adherence to the ACC/AHA treatment guidelines and patient outcomes.
The researchers identified 29,357 CRUSADE patients who had both levels of biochemicals taken within the first 36 hours of admission.
As would be expected, patients who had negative CK-MB and troponin levels (11.9 percent of the sample) had the lowest usage of the different therapies, and they had the lowest death rate -- 2.71 percent. At the other extreme, patients who were positive for both biomarkers (59.7 percent) had the highest usage of the therapies, as well as the highest death rate, 5.87 percent.
"In the two discordant groups, GP IIb/IIIa inhibitors were similarly used in less than 25 percent of the cases, while only slightly more than one-third of these patients received catheterization," Newby said. "This discrepancy occurs even though the troponin-positive/CK-MB-negative patients had a 4.45 percent death rate, compared to 2.95 percent rate for those who were troponin-negative/CK-MB-positive."
In 2001, Duke cardiologists showed that in terms of risk of future heart attacks, patients who were then considered lower risk -- those who were troponin-positive but CK-MB negative -- should in fact be treated as if they were high-risk patients.
"The results of out CRUSADE analysis shows that physicians -- for whatever reasons -- are not using therapies that we know can benefit high-risk patients," Newby said. "It is one of those cases where those who would stand to benefit the most from a therapy are not receiving it.
"As physicians, we don't always appreciate or interpret risk accurately," Newby continued. "One key to improving outcomes is for physicians to understand risk, and to understand that these therapies have been proven effective in clinical trials to reduce clinical events, particularly in high-risk patients."
CRUSADE is funded by Millennium Pharmaceuticals, Cambridge, MA, and Schering Corp, Kenilworth, NJ. Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, New York, provided an unrestricted grant in support of CRUSADE.