Straight to the Heart: Comparative Effectiveness Research Weighs Merits of Competing Cardiac Imaging Modalities
Three-vessel disease also explains the false negative nuclear imaging finding. SPECT MPI works physiologically to indirectly detect coronary artery disease by mapping the abnormal perfusion of blood from blocked arteries through the heart muscle and easily identifies perfusion deficits from one or two occluded vessels. But occlusions in three major vessels can produce balanced ischemia in the heart muscle making SPECT images appear normal—one of many reasons why Schoepf prefers CCTA, which allows clinicians to directly survey the coronary arteries for occlusion. "CT gives you a much more comprehensive picture of the patient's cardiovascular status," he says. Indeed, multiple clinical trials have confirmed the clinical efficacy of cardiac CT and SPECT MPI.
The next step is controlled randomized multi-center clinical trials to compare performance. Many cardiovascular imagers welcome upcoming comparative effectiveness trials designed to provide statistically valid head-to-head comparisons of the relative financial costs and clinical benefits of SPECT MPI, coronary CTA and other noninvasive cardiac imaging exams. Skepticism about cardiac CT runs high, despite evidence demonstrating the weaknesses of the imaging techniques that are suppose to identify patients who should be referred for cardiac catheterization and x-ray coronary angiography.
Multi-center efficacy trials, such as CORE64 and ACCURACY, published in 2007 and 2008, respectively, have demonstrated that CCTA accurately diagnoses significant coronary artery disease and can reliably rule out its presence and assess the risk of future myocardial infarction (MI) and cardiac death.
David Levin, MD, a professor of radiology at Philadelphia's Thomas Jefferson University Hospital, says enough evidence has already been collected to show that 64-slice or higher CCTA improves patient care and saves billions of healthcare dollars. "There is a better way than SPECT MPI to weed out patients who don't need catheterization. That way is coronary CTA."
Yet, efficacy trials don't consider the cost-effectiveness of emerging technologies. "The watch word among payors is data," offers Maurine Spillman-Dennis, senior director of economics and health policy at the American College of Radiology. "They want trials and outcomes data."
Competing modalities comparedThe clash between clinical- and cost-effectiveness has compelled medical researchers and policymakers to reconsider how medical technologies are assessed. Their consensus solution is comparative effectiveness research (CER), a method for weighing the relative clinical and sometimes financial merits of competing medical technologies.
"We have done great work in terms of defining the test performance [of cardiac CT] in term of accuracy," says Arthur E. Stillman, MD, PhD, director of cardiothoracic imaging at Emory University in Atlanta. "But we haven't done well in doing real comparative effectiveness trials."
CER can potentially answer the practical questions clinicians and policymakers pose when weighing the relative merits of competing technologies, according to Pamela K. Woodard, MD, head of advanced cardiac imaging at Washington University School of Medicine, St. Louis. "It will establish what coronary CTA is good for," she said. "In which clinical instances does it lead to better outcomes and cost savings?"
Congress contracted with the Institute of Medicine to solicit public and scientific opinion to develop a list of 100 initial CER priority topics. Two cardiac imaging issues appeared on the priority list. One called for studies comparing the effectiveness of traditional risk stratification methods for coronary heart disease and noninvasive imaging. The other recommended trials comparing the effectiveness of CTA and conventional angiography for assessing coronary artery stenosis in patients with moderate risk of coronary artery disease.
|Status of Four CER Cardiac Imaging Trials|
1. RESCUERESCUE, a randomized trial involving 4,300 adult patients with stable angina treated at 80 healthcare institutions, hypothesizes that CCTA will yield the same clinical outcomes as SPECT MPI over a two-year period and will be more cost-effective. Patients diagnosed with significant left main disease will immediately be referred for cardiac cath and possible revascularization. Participants with other positive cardiac findings will receive optimal medical therapy.
Patients will be monitored for up to two years for major adverse cardiac events (MACE) and revascularization. Researchers will measure relative costs and radiation exposure.
RESCUE follows the COURAGE Trial (Clinical Outcomes Utilization Revascularization and Aggressive Drug Evaluation), the 2007 study that found no difference in the MACE rate for patients with stable coronary disease, who received optimal medical therapy compared to patients who were treated with a percutaneous coronary intervention.
2. PROMISEPROMISE, a 200 site/10,000 participant trial, compares CCTA with functional stress test exercise ECG, stress echocardiography and stress nuclear imaging for patients at low-to-intermediate risk of coronary artery disease (CAD), who present in the emergency room with chest pain. Participants will be monitored for at least two years for the primary endpoints of death, MI, unstable angina and hospitalization and severe complications from cardiovascular procedures.
"We haven't done large scale randomized controlled trials of different testing strategies before, though at least 10 million people in the U.S. are in this clinical situation," explains Pamela S. Douglas, MD, principal investigator and professor of cardiovascular disease research at Duke University in Durham, N.C.
The noninvasive imaging strategies will be compared on the basis of primary clinical and secondary economic outcomes. The investigators hypothesized that information derived with anatomic testing will drive superior outcomes compared with information derived from functional testing.
PROMISE is scheduled for completion in 2015.
3. ACRIN PA 4005
The trial aims to estimate the rate of major cardiac events within 30 days of discharge for patients who did not have significant disease on CT scans. ACRIN PA 4005 is tracking relative costs and utilization of medical resources, hospital length of stay and additional ER visits for all subjects for one year.
Harold Litt, MD, chief of cardiovascular imaging at the Hospital of the University of Pennsylvania in Philadelphia plans to complete recruitment by July 2011 and publish results by March 2012.
4. ROMICAT IIROMICAT II (Rule Out Myocardial Infarction Using Computer Assisted Tomography) is a repeat performance to determine if a large randomized multi-center clinical trial can duplicate the results of a single-center experience.
ROMICAT I demonstrated that 64-slice coronary CT can reliably rule out acute coronary syndrome for patients at low or intermediate risk of acute coronary syndrome who presented to the emergency department with chest pain.
Ten medical centers will enroll 1,000 chest pain patients who fit the ROMICAT I clinical profile. By randomly selecting them to undergo CCTA or a traditional diagnostic workup, ROMICAT II will test whether CCTA significantly reduces the patient's hospital length of stay and its relative cost-effectiveness compared to the standard protocol.