The Lower the LDL, the Better
A small study involving 161 patients found that lowering LDL to <100 mg/dL actually caused regression of carotid intima-media thickness, a surrogate measure for atherosclerosis. The study from the Walter Reed Army Medical Center in Washington, DC, appears in this week’s issue of Circulation (2002;106:2055–2060).
In this single-center randomized study led by Allen J. Taylor, MD, Director of the Cardiovascular Research Cardiology Service at Walter Reed, patients were randomly assigned to treatment with either pravastatin (40 mg/d) or atorvastatin (80 mg/d). Blinded, serial assessment of the far wall of the distal common carotid artery was made over a 12-month period.
During the year, atorvastatin was more potent in reducing LDL. Patients in the atorvastatin group averaged 76 mg/dL, a reduction of 48.5% in LDL compared with 110 mg/dL (27.2% reduction) in the pravastatin group. During the same year, members of the atorvastatin group saw their carotid intima-media thickness reduced by 0.034 mm, whereas the change in the measurement was not statistically significant in the pravastatin group.
The authors concluded that reducing LDL markedly below 100 mg/dL with atorvastatin was superior to treatment with pravastatin in achieving this surrogate for atherosclerosis regression. They concluded that such lowering “supports the hypothesis currently being tested in ongoing randomized clinical trials that marked LDL reduction with synthetic statins may provide enhanced reduction in clinical coronary event rates.”
In an accompanying editorial (Circulation. 2002; 106:2039–2040), Prediman K. Shah, MD, from the Division of Cardiology and Atherosclerosis Research Center, Burns and Allen Research Institute, Cedars Sinai Medical Center, Los Angeles, Calif, also pointed out that several larger studies are now ongoing to study this issue.
He wrote: “The data provided by Taylor et al are of potential interest and could have significant implications for clinical practice. However, before we definitively conclude that ‘more’ (LDL-C lowering) means ‘less’ (atherosclerosis progression/clinical events), several points deserve emphasis.” He said that because the measurements were of carotid intima-media thickness rather than advanced atherosclerotic plaque, any conclusions about regression are inferential. Furthermore, the number of patients was small with a short follow-up, and the differences between the groups of patients who received the different drugs may be related to properties unique to each rather than the magnitude of lower LDL. He added that the benefits of aggressive lowering of LDL must be balanced against an increased risk of adverse effects, and the conclusions of this study must be accepted with some reservations.
Institute of Medicine Advocates More Protection of Human Research Participants
In a report released October 3, 2002, the Institute of Medicine (IOM) called for broader federal oversight of research that involved human subjects—whether publicly or privately funded.
In the report, the IOM called for federal government oversight of every kind of biomedical research through a research participant protection program.
“It is understandable that the public has come to perceive that research institutions put more emphasis on insulating themselves from liability than on protecting people from harm,” said Daniel Federman, chairman of the IOM committee that released the report and Senior Dean for Alumni Relations and Clinical Teaching and Professor of Medicine and Medical Education at Harvard Medical School, Boston, Mass. “There is no single cause for the errors and mishaps that unfortunately have resulted in the deaths of some research participants in recent years. Rather, a combination of stresses, weaknesses, and lack of accountability have strained the current hodgepodge of protections to the point that fundamental changes are needed to protect all participants and keep public trust from being irrevocably eroded.”
The IOM commissioned the report in the wake of the death of Jesse Gelsinger, who died in 1999 while participating in a gene therapy study at the University of Pennsylvania. The case, along with others at major institutions, highlighted deficiencies in the research subject protection system, including inadequate oversight and conflict of interest among those running the studies.
The committee proposed a system of interdependent elements involving investigators, the institutional staff charged with monitoring safety and data, boards that review the scientific and ethical integrity of research, and the research sponsor—all intertwined in a network designed to protect human subjects. The report can be accessed at http://www.nap.edu/books/0309084881/html./
Health Coverage Falls
The number of people without health insurance coverage rose 1.4 million between 2000 and 2001, according to data released by the US Census Bureau on September 30, 2002. The Bureau estimated that 41.2 million people in the United States were without health insurance coverage in 2001.
An estimated 14.6% of the US population had no insurance coverage in 2001, compared with 14.2% in 2000. Census bureau officials blamed the increase on a drop in employment-based insurance.
Young adults aged 18 to 24 remained the group that was least likely to be covered by health insurance in 2001. According to the Census Bureau, 28% of those in this age group lacked coverage.
According to a story in the Washington Post on September 30, 2002, health policy experts saw the numbers as a foreshadowing of more dramatic declines to come. They attributed the declines to rising unemployment, increasing medical inflations, and the number of states in which publicly funded insurance programs are outpacing the budgets.
In a released statement, Ron Pollack, Executive Director of Families USA, a patient advocacy group, said, “Last year, the Census Bureau reported that there were 38.7 million uninsured Americans in 2000. This year, the report provides a double whammy: it increases the estimate for 2000 from 38.7 million to 39.8 million and it estimates that the number of uninsured rose to 41.2 million in 2001. This new number means that there are more uninsured people than the aggregate population of 23 states plus the District of Columbia.
“The increased number of uninsured Americans is a forerunner of much larger increases to come. The confluence of 4 factors—much higher health care costs, employers passing on more of these costs to their workers, unemployment growth, and state cutbacks in Medicaid programs—all but guarantees that the number of uninsured people will skyrocket in the next few years.”