Even Patients With Low Levels of Heart Cell Death Should be Treated More Aggressively
CHICAGO -- Patients who test positive for even low levels of a specific biochemical marker of heart cell death in their blood are not being treated as aggressively as patients with higher levels, according to a new analysis by cardiologists at Duke University Medical Center.
They add that these patients, despite low biochemical marker levels, are still at high risk for early death and have just as much to gain from the aggressive use of medical and interventional therapies that have been proven effective by large clinical trials.
The biochemical marker analyzed, troponin, is a protein within heart muscle cells that leaks into the bloodstream when heart cell walls break apart during a heart attack, or myocardial infarction (MI). Although the American College of Cardiology (ACC) and American Heart Association (AHA) have recently recast the definition of heart attack by placing more emphasis on the results of troponin testing, many patients with low positive troponin levels are not receiving the treatments that would lessen their risk of death, according to the researchers.
"Our data shows that even low levels of troponin elevation are associated with a higher risk of early mortality," said cardiologist Matthew Roe, MD, of the Duke Clinical Research Institute. Roe presented the results of the study today (April 1, 2003) at the 52nd annual scientific sessions of the ACC. "While it makes sense that any amount of heart muscle death is a bad thing, it has not been proven -- until now -- in a large and comprehensive group of patients.
"Despite guidelines established by the AHA and ACC that link initial therapy selection to positive troponin levels, acceleration of acute treatment only occurs in patients with major troponin elevations," Roe continued. "These paradoxical results suggest that improvements in early cardiac care could reduce mortality in all patients with positive troponin levels."
For his analysis, Roe 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 AHA Guidelines). CRUSADE continuously gathers data from over 400 participating U.S. hospitals on treatments for patients with non-ST-segment elevation MI and unstable angina (collectively known as non-ST-segment elevation acute coronary syndromes -- NSTE ACS) and provides regular feedback to hospitals with the ultimate goal of improving adherence to the ACC/AHA treatment guidelines and patient outcomes.
While similar studies have been conducted on patients suffering from acute ST-segment elevation MI, CRUSADE targets a different, but just as important, group of high-risk heart patients. CRUSADE patients will typically arrive at emergency rooms with chest pain (angina), but often will not have telltale signs of an MI on the initial electrocardiogram and may only be diagnosed with a heart attack when the results of initial troponin testing are reported a few hours later.
It is estimated that about 1.3 million Americans are hospitalized each year with NSTE ACS. While patients with acute ST-segment elevation MI are at higher risk of dying within 30 days of their hospital stay, patients with NSTE ACS actually have a higher risk of dying six months and one year after initial hospital presentation. Despite these high-risk features, previous quality improvement studies for patients with heart attacks have only focused on patients with acute ST-segment elevation MI.
Roe and colleagues divided the 21,694 eligible patients from 342 participating hospitals into four groups based on the peak levels of troponin measured within 24 hours of hospital presentation: normal, mild, intermediate and major. They then analyzed how these patients were treated and their outcomes while hospitalized.
The analysis showed that 6.1 percent of the patients with major elevation in troponin levels died in the hospital, compared with 4.6 percent for those with intermediate elevations, 4.3 percent for mild elevations, and 2.8 percent for those with normal levels. These findings demonstrate that patients with even mild troponin elevations have a two-fold increase in the risk of early, in-hospital mortality, Roe said.
Patients with major troponin elevations were most likely to receive acute medical therapies with proven benefits -- aspirin, beta blockers, heparin, glycoprotein IIb/IIIa inhibitors and clopidogrel -- with rates that decreased as the troponin levels decreased.
"Those patients with major elevations are getting these drugs at fairly high rates, but there is still room for improvement, even in this group of patients," Roe said. "But physicians should have a much lower threshold of in terms of initiating aggressive treatments for patients with any elevation of troponin levels, since all patients with troponin elevations are at a higher risk of early mortality."
Just as they did with medical therapies, the researchers found underutilization of invasive interventions such as cardiac catheterization and angioplasty. Patients with major troponin elevations received angioplasty the most at 40 percent, followed 35 percent for those with normal levels and 30 percent for those with mild and intermediate elevations. For catheterization, 70 percent of patients with major elevation underwent the procedure, followed by 64 percent of normal patients, 61 percent of intermediate-elevation patients and 58 percent of those mild elevations.
"Out in the community, physicians typically don?t believe that lower levels of troponin are worrisome and that the measurements may be inaccurate," Roe said. "They usually wait until the troponin levels get higher before they take definitive action. But those actions run counter to what the national guidelines, and this study, recommend."
Ultimately, CRUSADE aims to include 60,000 high-risk NSTE ACS patients at over 400 U.S. hospitals. CRUSADE is the first study to collect this kind of data on so many patients with the goal of actually influencing practice patterns and improving clinical outcomes, Roe said.
CRUSADE is coordinated by the Duke Clinical Research Institute and is funded by Millennium Pharmaceuticals, Cambridge, MA, and Schering-Plough Corp., Kenilworth, NJ.