A joint advisory committee of the FDA in mid-July recommended against approving a low-dose formulation of the cholesterol-lowering drug Mevacor for over-the-counter sale. Made by Merck (Whitehouse Station, New Jersey), the drug is generically known as lovastatin, and the company was seeking OTC approval for its 10 mg tablets. However, the Nonprescription Drug and Endocrinologic and Metabolic Drug Advisory Committees voted 11-1 against approval, asking Merck to provide additional information to demonstrate consumers' ability to use the product with minimal instructions.
The company said in a statement following the thumbs-down vote, "It is important to note that an Rx-to-OTC switch candidate representing a new therapeutic category rarely receives an initial recommendation for approval from an FDA advisory committee. Merck will continue to work with the FDA to discuss the criteria for approval of an OTC-medication to lower cholesterol." Eve Slater, MD, senior vice president, clinical and regulatory development, Merck Research Laboratories, said, "We feel very positive about the endorsement of Mevacor's safety and having advanced the dialogue and understanding on this issue."
However, the panel members said they were not convinced that the drug would produce any health benefit for the 15.5 million Americans with mildly elevated cholesterol, the group which Merck said would benefit most by having an over-the-counter treatment. The target group outlined by Merck includes men aged 40 and older and postmenopausal women who do not have established cardiovascular disease or diabetes and whose total cholesterol levels are 200-240 mg/dl and low density lipoprotein (LDL) levels are greater than or equal to 130 mg/dl. But according to panel chairman Eric Brass, MD, Merck's studies did not offer evidence of significant clinical benefit.
Race, location key to female cardiac deaths
Data provided by the Centers for Disease Control and Prevention (Atlanta, Georgia) and the World Health Organization (WHO; Geneva, Switzerland) have shown extreme differences in heart disease death rates for U.S. women, depending upon race and geographical location. Published in the June issue of the Journal of Women's Health & Gender-Based Medicine, the study was conducted by the University of Pittsburgh Graduate School of Public Health (GSPH). Investigators found a wide range in these figures: a seven-fold difference in mortality from coronary heart disease (CHD) among American women aged 45 to 54 – 125 deaths per 100,000 black women in Arkansas vs. 17 deaths per 100,000 among white women in Colorado. Overall, researchers found black women had rates that were nearly three times those of white women, with overall mortality rates highest in the deep south and lowest in western and eastern states.
For black women, mortality rates for CHD were highest in Arkansas (124/100,000), Louisiana (113/ 100,000) and Pennsylvania (108/100,000) and lowest in New Jersey (45/100,000), Maryland (49/100,000) and Georgia (57/100,000). For white women, rates were highest in Louisiana (55/100,000), Mississippi (53/100,000) and Oklahoma (50/100,000) and lowest in Minnesota(22/100,000), Washington (18/100,000) and Colorado (17/100,000). Akira Sekikawa, MD, PhD, a research fellow and principal investigator of the study, said, "This is the first study to focus on how geographic and racial differences affect heart disease mortality among women in the 45-to-54 age bracket – a critical time when women experience many physiological changes that can ultimately affect the heart."
Wound healing, atherosclerosis and ....
Atherosclerosis has traditionally been regarded as blockage of the coronary arteries feeding the heart by fatty buildup of clot-forming plaques. Much of the blame for this presumed process lay on excess cholesterol intake. But a commentary in the June 20, 2000, Proceedings of the National Academy of Sciences (PNAS) proposes a different indictment: "Atherosclerosis can now be viewed as a problem of wound healing and of chronic inflammation." That comment, by microbiologist Richard Phipps at the University of Rochester (Rochester, New York), bears the title: "Atherosclerosis: The emerging role of inflammation and the CD40-CD40 ligand system." The PNAS paper in the same issue – the object of Phipps' commentary – is titled "Inhibition of CD40 signaling limits evolution of established atherosclerosis in mice." Its authors are in the cardiovascular division of Harvard-affiliated Brigham and Women's Hospital (Boston, Massachusetts). For 13 weeks, the co-authors fed 30 young mice a high-cholesterol diet calculated to promote atherosclerosis. Then, they treated one group of those animals with a monoclonal antibody against the CD40 molecule paired with its ligand, CD40L. This proinflammatory dyad galvanizes the immune system's B and T cells to release cytokines, which make for the blood-vessel walls where atheromas grow.
When the paper's co-authors autopsied the blood vessels of their treated mice after 26 weeks, they found that "interfering with CD40 signaling did not regress, but did inhibit the progression of already established atherosclerotic lesions." "Disrupting the CD40-CD40L system," Phipps observed, "has generated much excitement." But he concluded his commentary with a caveat: "Obviously, there is a need for caution, because interference with the CD40-CD40L system is immune suppressive."
... sleep blood flow linked to cardiac events
Israeli researchers using a device that non-invasively measures peripheral arterial tone (PAT) recently identified a relationship between reduced peripheral arterial flow during rapid eye movement (REM) sleep and increased incidence of cardiac events in the early morning. Reported in the June issue of Nature Medicine, the study described the use of PAT measurements throughout the night in nine normal adults (ages 25-40) and 17 patients with light to moderate sleep apnea (age 35-60). In both groups, PAT signals indicated that arterial flow was most constricted during REM, with these signals also useful in determining REM onset and duration. "Peripheral arterial tone has been shown to be an accurate reflection of the autonomic nervous system function," said principal investigator Peretz Lavie, PhD, of the Technion (Haifa, Israel) faculty of medicine and head of the Technion Sleep Laboratory (Caesaria, Israel), adding that this system in turn regulates various physiological systems. Thus, measuring increased peripheral blood flow resistance could be used as a stress test for the heart, he said.
The PAT is measured at the finger, where the diameter of the peripheral arteries is under direct control of the sympathetic branch of the autonomic nervous system. The PAT signal there offers "a sensitive and accurate window to the autonomic nervous system's level of activation." Incorporating a multi-cell pneumatic-optic finger probe, the study device was developed at the Technion by Robert Schnall, MD. "Two novel features of this new device are the unique multi-cell construction of the finger probe to prevent accumulation of venous blood in the fingertip, and advanced digital signal processing algorithms to interpret the signal," Schnall said.
Study reports 'no pain' MIs
Thirty-three percent of patients diagnosed as having a myocardial infarction (MI) did not have chest pain, according to a recent study supported by the Agency for Healthcare Research and Quality (AHRQ; Washington) and published in the June 28 issue of the Journal of the American Medical Association. Researchers at the University of Alabama at Birmingham found that those MI patients without chest pain not surprisingly were less likely to receive prompt, less-aggressive treatment and had an increased chance of in-hospital mortality, compared to those experiencing chest pain.
The researchers concluded that more emphasis needs to be placed on national public health initiatives educating the public and medical professions to the fact that chest pain is not necessarily a key MI feature. The report follows another recent AHRQ study that concluded that patients treated at hospitals experienced in performing large numbers of primary angioplasty procedures have higher survival rates.