A New Route to Revascularization
Intramyocardial injections of stem cells derived from bone marrow were safe and seemed to indicate a potential for improvement in the patients with heart failure who received them, said members of an international team that reported its results in this week’s issue of the journal Circulation (Circulation. 2003;107:2294–2302). This work was based on several years of research in experimental animal models led by James Willerson, MD, Yong-Jian Geng, MD, and Emerson Perin, MD,at the Texas Heart Institute in Houston, Tex.
“The most important result is that the procedure is safe,” said Emerson Perin, MD, PhD, of the Texas Heart Institute, who was lead author of the study. Dr Perin presented his results during the scientific sessions of the American College of Cardiology in Chicago, Ill, at the beginning of April. “There were no major procedural complications or periprocedural complications,” he said.
“Symptoms improved in terms of heart failure and angina class,” he said. “There was improvement in functional capacity. Many [patients] had dramatic changes in terms of lifestyle.”
The test was carried out at the Procardiaco Hospital in Rio de Janeiro, Brazil, by clinical research teams from that hospital and the Texas Heart Institute. Fourteen patients received the stem cell injections, and 7 patients served as controls.
All the patients had severe coronary artery disease with heart failure, and none were candidates for standard revascularization techniques, said Dr Perin. At baseline, all patients received complete clinical and laboratory evaluations, exercise stress tests, 2D Doppler echocardiogram, single-photon emission computed tomography perfusion scan, and 24-hour Holter monitoring.
For those patients who received the treatment, bone marrow mononuclear cells were harvested, isolated, washed, and suspended in saline before injection by NOGA catheter. Electromechanical mapping identified viable heart muscle. A total of 15 injections of 0.2 cc were given.
Treated and untreated patients were followed up noninvasively for 2 months; treated patients underwent invasive follow-up at 4 months. Patient population demographics and exercise test variables did not vary between treatment and control groups. Serum creatinine and brain natriuretic peptide levels varied in laboratory evaluations at follow-up. Both measured higher in the control patients.
At 2 months, the treatment group showed a significant reduction in total reversible defect and improvement in global left ventricular function. The difference between control and treatment groups was also significant. Evaluations were carried out by quantitative single-photon emission computed tomography analysis. At 4 months, the treatment group showed an improvement in ejection fraction from 20% to 29% and a reduction in end-systolic volume. Mapping carried out on the heart muscle showed significant mechanical improvement of the injected segments.
“The implications for heart failure treatment are very significant, if these findings can be confirmed in larger studies,” said Dr Perin. “The promise of stem cell therapy is exciting. This therapy is safe and suggests there may be some potential for this kind of therapy to help patients with heart failure. This is only the first step. We will continue to expand our efforts to bring this form of therapy to the United States.”
First Drug-Eluting Stent Approved
The US Food and Drug Administration (FDA) has approved the first drug-eluting stent to be used in angioplasty. As expected, the Cypher Sirolimus-Eluting Coronary Stent (Cypher stent) made by Cordis Corporation of Miami Lakes, Fla, got the federal nod.
The stent is covered by the drug sirolimus or Rapamune (Wyeth-Ayerst), which selectively targets proliferating cells by zeroing in on an enzyme (TOR) that is crucial to cell proliferation. By blocking proliferation early in the cell cycle, the drug returns cells to their resting state, allowing the blood vessel to heal completely. The drug also reduces activity of inflammatory cells. Unlike cytotoxic drugs, sirolimus is not known to destroy cells.
The Cypher stent slowly releases the drug. In clinical studies, it is known to significantly reduce the rate of restenosis. The low rate of restenosis seen in early studies rocked the interventional cardiology community at the European Society of Cardiology in the year 2000. Previously, high rates of restenosis had made angioplasty less effective than had been expected when the procedure was first used. Restenosis rates have been as high as 30%.
“Today’s approval represents a significant step forward in the treatment of heart disease,” said US Health and Human Services Secretary Tommy Thompson on the day that approval was announced. “Patients who receive this device will need fewer repeat operations to unclog arteries, which can make a real difference in the quality of their lives.”
“Drug-eluting stents combine drugs with medical devices to provide more effective care for many patients with heart disease,” said FDA Commissioner Mark McClellan, MD, PhD. “FDA is working to make sure its regulatory procedures encourage the quick and efficient approval of such safe and effective combination products.”
The FDA is requiring that Cordis conduct a 2000-patient post-approval study and continue to evaluate patients from ongoing clinical trials to assess the long-term safety and effectiveness of the Cypher stent and to look for rare adverse events that may result from the use of this product.
The Value of Pictures in Prevention
Using electron beam tomography (EBT) as a tool to encourage reduction of cardiovascular risk was not effective in a study conducted by military physicians, according to a report that appears in the May 7, 2003, issue of The Journal of the American Medical Association (JAMA. 2003;289:2215–2223). The researchers, led by Patrick G. O’Malley, MD, MPH, of Walter Reed Army Medical Center in Washington, DC, concluded that primary prevention programs should continue to focus on detection and management of modifiable risk factors and not on images that demonstrate risk.
In their study, the researchers enrolled 450 asymptomatic, active-duty US Army personnel aged 39 to 45 years. Patients were randomly assigned to 1 of 4 groups in the study. Two groups received their EBT results and were randomized to receive intensive case management (ICM) or usual care. In two other groups, subjects were randomized to ICM or usual care, but their EBT results were withheld.
The researchers had hypothesized that showing patients a picture of the anatomy of their coronary arteries would motivate them to change their risk factors to reduce the risk of cardiovascular disease. Patients were followed up for 1 year. The primary outcome measure was change in a composite measure of risk, the 10-year Framingham Risk Score (FRS).
“Comparing the groups who received EBT results with those who did not, the mean absolute risk change in 10-year FRS was +0.30 vs +0.36. Comparing the groups who received ICM with those who received usual care, the mean absolute risk change in 10-year FRS was −0.06 vs +0.74,” the authors write. “In multivariable analyses predicting change in FRS, after controlling for knowledge of coronary calcification, motivation for change, and multiple psychological variables, only the number of risk factors and receipt of ICM were associated with improved or stabilized projected risk. Our findings show that in an asymptomatic population at an appropriate age for cardiovascular risk screening, the addition of anatomically based subclinical coronary disease diagnosis using EBT does not substantially affect coronary risk profile.”
They further concluded: “Even if use of a diagnostic technology were motivational, it is unlikely to be optimally used without the clinical expertise to interpret the significance of the results. The current widespread use of a model of self-referral for atherosclerosis screening does not formally couple such decision making and interpretation with a regular health care practitioner and, thus, may be largely ineffectual as an intervention to incrementally alter cardiovascular risk.”
In an editorial in the same issue, Philip Greenland, MD, of the Feinberg School of Medicine at Northwestern University in Chicago, Ill, said that motivating patients to change their risk profiles is an ongoing problem (JAMA. 2003;289:2270–2271). He said, “Despite well-defined strategies for reducing CHD [coronary heart disease] risk factors, clinicians find that many patients at risk appear to lack the interest or motivation to undertake intensive risk factor treatment efforts. Awareness studies show that even now large proportions of Americans have never had risk factors measured, and many who have had these measured do not achieve acceptable levels of control.”
“Based on the [O’Malley] trial results, intensive case management emerges as a viable primary prevention approach, while the role of EBT remains uncertain. The report by O’Malley et al will hopefully encourage design and execution of more randomized trials to define specific roles for EBT in risk prediction,” Dr Greenland wrote.
Paying More and Getting Less
Americans pay more for their health care but receive less than citizens of any other industrialized nation, according to a report from researchers in the May/June issue of the journal Health Affairs (Health Affairs. 2003;2:89–105).
For example, US expenditures for health care were 44% higher than those of Switzerland, the nation with the next highest per capita healthcare costs in the year 2000. However, Americans went to the physician less often and had shorter hospital stays than citizens of other industrialized nations, according to the study.
According to the study, the price differential is explained by higher prices for healthcare goods and services in the United States.
“As a country, we need to ask whether increased spending means more resources for patients or simply higher incomes for health care providers,” said Gerard Anderson, PhD, the study’s lead author. He is a professor in the Departments of Health Policy and Management and International Health at Johns Hopkins University School of Public Health. “Policymakers should assess exactly what Americans are getting for their greater health care spending.”
Dr Anderson and his colleagues compared health systems data for 30 industrialized countries in the Organization for Economic Cooperation and Development in the year 2000 (the most recent information available). They compared pharmaceutical spending, health system capacity, and use of medical services.
Americans spent $4631 for health spending in the year 2000—an increase of 6.3% over 1999. Spending in the year 2000 was 83% higher than that of Canada and 134% higher than the median of $1983 spent by other members of the group studied. The gap between the United States and the other industrialized countries widened between 1990 and 2000, the decade in which managed care was ascendant.
Healthcare spending in the United States was 13% of the gross domestic product (GDP), whereas it was only 10.7% of GDP in Switzerland and 9.1% in Canada. The median for all the nations in the group was 8%.
Americans spent $2580 out of their own pocketbooks, more than 5 times the median amount of $451 for the other nations. In addition, 56% of US healthcare spending was financed from private sources, the greatest percentage of any of the nations.
Public financing of health care from sources such as Medicare or Medicaid was 5.8% of GDP, similar to the 5.9% of GDP spent by the other nations. However, the United States spent $2051 of public funds per person, much higher than the median of $1502 spent by the other countries. In most nations other than the United States, public healthcare expenditures take care of everyone.