Noted experts fear Vioxx-like scenario is about to be repeated with potentially deadly results for those who would take the drug that is about to be approved for sale.

An eagerly awaited diabetes drug, which is nearing final approval by the FDA, significantly increases the risk of heart attacks, strokes, or death, researchers reported in a study published in the Journal of the American Medical Association yesterday.

The study is yet another situation that raises serious questions concerning the reliability of the FDA’s drug approval process and whether it is unduly biased in favor of the pharmaceutical industry.

Muraglitazar, which would be marketed as Pargluva by Merck and Bristol-Myers Squib, was recommended for approval last month by an advisory committee from the Food and Drug Administration.

The drug was highly anticipated by diabetes experts because it tackles both high cholesterol and high blood sugar; two serious problems suffered by the 18 million people with diabetes who are at an elevated risk of developing heart disease.

The new study used the very same data the FDA panel and staff examined. While the FDA panel voted 8-1 for approval of the drug, the study researchers identified several serious health concerns about the drug based on that data.

Looking at 2,374 patients who took Pargluva, and 1,351 people who took either a placebo or a rival drug, Actos, researchers found that Pargluva-treated patients had almost a threefold greater risk of heart failure, heart attack, stroke, and death.

"Ten of 1,000 patients would die, have a heart attack or a stroke," said lead author Steven Nissen of the Cleveland Clinic. "Those are serious irrevocable events."

The new study comes from the highly respected researchers at the Cleveland Clinic, the same team that broke the story on the cardiovascular dangers of Merck’s anti-inflammatory drug Vioxx.

Dr. Nissen has often been an outspoken critic of the methods and motives of the pharmaceutical industry and the FDA with respect to the entire drug approval process and after-approval monitoring of drugs for dangerous side-effects.

"These findings are particularly concerning because the significant excess of adverse events was observed after only limited drug exposure ranging from 24 to 104 weeks," Nissen, and colleagues report. "Real-world exposure would likely substantially amplify the risk. Taken as a whole, these data demonstrate that [Pargluva], if approved by the FDA, would constitute an unacceptable patient hazard."

The FDA announced that Pargluva was ready for release on the market earlier this week.
And due to the severity and prevalence of diabetes, there is no doubt that the drug’s manufacturers and marketers are eager to capitalize on the demand for the dual-acting, potential powerhouse drug.

But at the same FDA advisory committee meeting where the drug was recommended for approval by a vote of 8-1, even the FDA’s own analysts identified evidence of cardiac risk.

In a scenario similar to the Vioxx narrative, however, the analysts did not highlight this cardiac risk to patients as significant, except in cases where the drug was used in conjunction with other therapies.

Experts from Bristol-Myers concluded that there was no significant increase in heart risk for patients. The analogy to the Vioxx debacle is inescapable. (As Yogi Berra would say; “This is like deja vu all over again.”)

The risks posed by Pargluva may not end with cardiovascular problems. A JAMA editorial by James M. Brophy, MD, PhD, of McGill University in Montreal, released along with the Cleveland Clinic’s report, says that patients who took Pargluva could be as much as three times more likely to get cancer than patients who took placebos, and that more widespread use could cause this link to grow significantly.

Brophy agrees with Nissen and the research team at the Cleveland Clinic’s recommendation of a wide-scale, pre-marketing safety trial to further examine Pargluva.

The potential for Pargluva and other drugs like it is vast and offers hope to the many millions of Americans who suffer the life-threatening diabetes. But a hasty or premature release of the drug to eager patients, without fully understanding or revealing the significant health risks, could have devastating consequences.

In the wake of the law suits and backlash against Merck and the FDA over the Vioxx scandal, the pharmaceutical industry as well as the FDA must recognize the simple fact that they each owe the public (and not investors or contributors) the highest duty to take every precaution before releasing a potentially harmful prescription drug.

Researchers at The Cleveland Clinic recently completed an analysis of clinical trials on muraglitazar (Pargluva), a new diabetes drug, finding that it doubles the risk of death, heart attack, and stroke.  

The results appeared in Thursday’s Journal of the American Medical Association (JAMA).  Because of the study’s potential impact on public health, the journal expedited the release of the study and published it along with an editorial.

The study’s lead author is Steven Nissen, M.D., Medical Director of the Cardiovascular Coordinating Center at The Cleveland Clinic, and a nationally recognized expert in intravascular ultrasound imaging.

Muraglitazar was developed by Bristol-Myers Squibb and Merck & Co.  It was evaluated by an advisory committee of the Endocrine and Metabolic Diseases Division of the FDA on September 9, 2005.  The committee voted eight to one recommending approval of the drug for use in the treatment of patients with Type 2 diabetes, the most common form of the disease.

Dr. Nissen and his co-authors analyzed the publicly available clinical trial data reviewed by the FDA Advisory Committee and found that the combined incidence of death, heart attack, and stroke was 2.23 times higher in patients treated with muraglitazar, compared with patients receiving either a placebo or the diabetes drug pioglitazone.

Heart disease is the leading cause of death in patients with diabetes, accounting for more than 80% of mortality in this group.  “Muraglitazar carries an unacceptable risk of heart-related complications and should not be approved until more safety data are available,” Dr. Nissan said.  

The study raises serious questions about the FDA approval system.  The only heart specialist on the FDA panel of experts convened to consider the approval of muraglitazar recused himself because of a conflict of interest.  In recent months, Congress has taken a heightened interest in how the FDA selects panel members for its advisory committees.

Catherine DeAngelis, JAMA’s Editor, agreed with Nissen’s call for further research and questioned why the FDA, the organization that is responsible for looking after the safety of the public, did not ask for additional testing prior to the drug’s approval.

The CPSC has announced the voluntarily recall of In-wall amplified volume control keypads manufactured in Taiwan by Dana Innovations, of San Clemente, California. Consumers should stop using the product immediately.

The amplifier in the keypad can overheat, posing a burn or fire hazard. Dana Innovations has received one report of overheating. There are no reports of injury or property damage.

The recalled controls were sold under the brand names Architectural Audio and HomeTech, and were professionally installed as part of whole house audio systems.

The switch plate covers for the recalled systems are white or almond, and “aVc” (amplified volume control) is imprinted above the volume control. They have the following model numbers:

Brand                         Model Numbers
Architectural Audio     20127
Architectural Audio     20128
HomeTech                  10114
HomeTech                  10115

The model number is not visible to the consumer, and consumers are instructed not to remove the keypads from the wall to look for a model number. All serial numbers are included in the recall.

The controls were sold through custom installation dealers and through homebuilders nationwide from May 2003 through June 2005 for about $150.

Consumers should turn off and stop using these amplified volume control keypads immediately, and contact Dana Innovations to arrange for a free replacement. Dana Innovations distributors are directly contacting consumers with the recalled systems.

For further information, call Dana Innovations toll free at (888) 484-6782 between 7 a.m. and 5 p.m. PT Monday through Friday.

The so-called “Cheeseburger bill” was overwhelmingly approved by the House of Representatives on Wednesday, Oct. 19th. 

The bill’s official name is the Personal Responsibility in Food Consumption Act, and it prevents frivolous obesity lawsuits against the manufacturers, distributors or sellers of food or nonalcoholic beverage products.

This is the second time that the Cheeseburger bill has been passed by the House.  It was originally passed in March 2004, but it did not come up for a vote in the Senate.  Both the House of Representatives and the Senate must approve a bill before it can become law.  The bill’s future is again uncertain as the Senate often blocks House-passed measures that cap legal damages or protect particular industries from lawsuits.

The food liability bill passed 306-120 on Wednesday, and proponents hailed it as a significant political victory for President Bush, who has sought to reduce civil suits.  Democrats called the bill a vehicle to hurt trial lawyers and help the multibillion-dollar food industry.

Obesity is an increasing medical problem in the United States, and proponents of the lawsuits have hoped to pressure food manufactures and distributors into providing more prominent health advisory information.  They believe that additional health warnings on products would change consumer behavior.

The bill’s sponsor, Representative Ric Keller (R-FL), is a strong advocate of “common sense and personal responsibility”, but Representative Bernard Sanders (I-VT) voted against the measure, saying that it sought to protect large corporations from legitimate consumer lawsuits.

Popular antipsychotic drugs may increase the risk of death when given to people with dementia, according to an analysis done by researchers at the University of California.

The research team analyzed 15 trials involving about 5,000 patients to determine if there was a correlation between the use of the antipsychotic drugs and an increased risk for death.  During the trails 3,353 patients took the antipsychotics and 1,757 were given placebos.  The researchers found that the risk of death rose from 2 percent to 3 percent for patients taking the antipsychotic drugs.

The research team, led by Lon Schneider, professor of psychiatry, neurology, and gerontology in the Keck School at USC, studied the correlation between aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal) and an increased risk for death.  There were 188 deaths associated with the antipsychotic drugs compared to 40 deaths associated with the placebos.

When the specific drugs were examined individually, there was no significant difference between the risks conferred by one drug over another.  The researchers noted that the differences “could not have been recognized by examining any individual trial.  The events were too sparse and the trials too small to be able to meaningfully assess for a dose response that might make attribution more compelling.”

According to the Washington Post, about a third of the 4 million to 5 million Americans with degenerative brain disorder are given antipsychotic drugs.  The drugs are approved for the treatment of psychosis in adults, but have not been specifically approved for use among elderly patients with dementia.

Mr. Schneider and his team found that most of the deaths came from cardiac problems or respiratory disorders.  He said that the drugs might increase the risk because they sedate patients and confine them to bed for longer periods, making them more likely to develop infections.

The analysis appears in the October 19 issue of the Journal of the American Medical Association.

Recent studies suggest that stomach-shrinking surgery is more dangerous than had been thought especially for men, the elderly, and people with conditions such as hypertension.

A study of 16,155 Medicare patients by Dr. David Flum of the University of Washington, published in the Journal of the American Medical Association, also found less experienced surgeons are putting patients at risk.

According to Flum, while patients are told the mortality rate is approximately one in 500 (.2%) to one in 1,000 (.1%) it can be considerably higher for specific groups such as those over the age of 65 and those who are disabled by a range of problems including obesity where "the risk of death is more like one in 50" (2%).

Flum’s study found 11% of patients over 65 died after stomach-shrinking surgery, a mortality rate higher even than that following open-heart surgery.

Men were found to be twice as likely to die as women, with a mortality rate of 7.5 % within a year of their surgery. (Women make up about 80% of the patients undergoing the procedure).

The death rate after 30 days was 2% for Medicare recipients. After 90 days, that rate was 2.8% and after a year, 4.6%t. This study also found the death rate was 1.6 times higher when done by a surgeon who performed a low volume of bariatric surgeries.

"Among Medicare beneficiaries, the risk of early death after bariatric surgery is considerably higher than previously suggested and associated with advancing age, male sex, and lower surgeon volume of bariatric procedures," wrote the study authors.

In a related study, re-hospitalization rates within a year following the surgery were found to be as high as 19%, while another said bariatric surgery has increased substantially since 1998 when only 13,365 procedures were performed.

The latter estimated 130,000 procedures would be performed in the United States in 2005. The number is expected to rise to 218,000 by 2010. A large number of these patients are women, and nearly two-thirds live in neighborhoods with the highest household incomes.

The increase in procedures corresponds with the quadrupling of the obesity rate between 1986 and 2000. According to Heena Santry of the, University of Chicago, about 5% of U.S. adults are “morbidly obese” having a body mass index of 40 or higher.

The most commonly performed bariatric surgery is Roux-en-Y gastric-bypass where the stomach is made smaller and a part of the small intestine is bypassed so that fewer calories and nutrients are absorbed. Among the risks from this procedure are infection, hernia, and long-term nutritional deficiencies.

Dr. Edward Livingston, chairman of gastrointestinal and endocrine surgery at the University of Texas Southwestern School of Medicine and chairman of the bariatric surgery work group for the Department of Veteran’s Affairs national health care system said, "I was not surprised by these findings. These studies are really a very small piece of the overall picture for bariatric surgery."

According to Livingston; "Bariatric surgeries result in weight loss, but they can result in complications and death. They can improve the complications of obesity and quality of life, and they may increase longevity." He reminded patients, however, that the decision about whether to have the surgery is a complicated one, and needs to be made on a fully informed, case-by-case basis.

Clearly, the elevated risks of death and other serious complications of bariatric surgery in particular classes of people is a factor that should be explored and explained to prospective patients especially when they belong to one or more of those higher-risk groups.

According to reports in the Wall Street Journal and MSNBC, the U.S. Food and Drug Administration (FDA) is taking a hard look at the use of anti-bacterial soaps.

In preparation for an October 20th meeting on the topic, the FDA’s Nonprescription Drugs Advisory Committee issued a number of documents on Monday detailing the safety concerns of those who argue that antibacterial products do more harm than good, creating resistant bacteria.  A committee of experts will meet on Thursday to examine whether the FDA needs to limit the use of antibacterial products by consumers.

The committee will be looking at the use of these products by healthy consumers, as opposed to people in the healthcare and food service industries.  In their briefing documents, the FDA said that they had not found any medical studies that definitively linked antibacterial products to reduced infection rates.  The committee will consider if there is evidence that antibacterial products pose long-term hazards, and whether they should recommend that the FDA issue restrictions or warnings on the sales and labeling of these products.

According to the Journal, any moves by the FDA could affect hundreds of products that are on store shelves.  Manufacturers have introduced 253 antibacterial products in the United States so far this year, and over 300 new products hit American shelves in 2004.

Manufacturers of these products disagree that their products cause health risks, and they point to studies that back up their view.  Other studies, however, point in the opposite direction.

A recent study done by the Centers for Disease Control (CDC) takes both sides of the argument.  Scientists recorded the development of bacteria in 224 households for a year.  No significant increase in resistant bacteria was found, nor did it find that antibacterial soap led to healthier homes than regular soap.  In its briefing papers, the FDA says “current data are conflicting and unclear.”

In addition to looking at the issue of resistant bacteria, the committee will also consider whether the synthetic materials in some soap poses an environmental hazard when they go down the drain, and whether the use of antibacterial soaps may leave homes too clean for children, who need some exposure to bacteria to develop a healthy immune system.

Researchers announced some surprising results at this weeks meeting of the American Society for Reproductive Medicine.  According to BBC News, several scientists reported that a high number of abnormal embryos are being produced by young healthy women.

Three U.S. studies were presented at the meeting.  The first was a study done by Dr. Jeffrey Nelson of the Huntingdon Reproductive Center in California.  Using an IVF check technique called PGD (preimplantation genetic diagnosis), Dr. Nelson screened 289 embryos from 22 egg donors, all of whom were healthy and under the age of 30.  He found that 42% of the embryos had abnormal chromosomes.

Dr. Peter Nagy and his colleagues at Reproductive Biology Associates in Atlanta compared the rate of chromosome abnormality between younger (under 35) and older (over 38) women.  Nearly two-thirds of the embryos produced by the younger set of women had abnormalities, and the number jumped to nearly three-quarters among the older women.

The third study came from the Shady Grove Centre of Preimplantation Genetics in Maryland.  They found that eggs from healthy donors, whose ages spanned from 21 to 31, had a 52% chance of genetic abnormality.

Until these studies, many health care providers thought that eggs from younger women were more likely to be free of abnormal chromosomes.  Dr. Nagy stated that the defects should not be present in such a high proportion of patients.  

According to Canada’s The Gazette, researchers aren’t sure what’s causing the degeneration, but suggest culprits may include genetic predisposition, environmental factors, or the in-vitro fertilization process itself.

Researchers stated that the rate of problematic IVF embryos mirrors the real world, where it’s estimated that over 60% of pregnancies are lost before a woman even realizes that she is pregnant.

The Food and Drug Administration (FDA) and Eli Lilly have notified healthcare professionals of a significant revision to the PRECAUTIONS/Hepatotoxicity section of the prescribing information for Cymbalta (duloxetine hydrochloride); Lilly’s antidepressant indicated for treatment of major depressive disorder and diabetic peripheral neuropathic pain.

Cymbalta, which already carries a Black Box Warning regarding “Suicidality in Children and Adolescents,” is now linked to post-marketing reports of hepatic injury (including hepatitis and cholestatic jaundice) that suggest “patients with preexisting liver disease who take duloxetine may have an increased risk for further liver damage.”
The FDA’s letter and the new Cymbalta label are posted online at http://www.fda.gov/medwatch/safety/2005/safety05.htm#Cymbalta.

The new labeling extends the Precaution against using Cymbalta in patients with substantial alcohol use to include those patients with chronic liver disease. It is recommended that Cymbalta not be administered to patients with any hepatic insufficiency.

"Some of these reports indicate that patients with preexisting liver disease who take duloxetine may have an increased risk for further liver damage," Lilly said in its letter to doctors dated October 5.

Reports that serious patient injuries and death can be caused by improper injection procedures, Boston Scientific Corporation has recalled all ENTERYX® Procedure Kits and ENTERYX® Single Pack Injectors. 

Prescribed for gastroesophageal reflux disease (GERD), ENTERYX® is injected by a physician into the inside muscle wall of the patient’s esophagus.

The liquid then thickens into a sponge-like substance helping to block stomach acids and prevent them from entering the esophagus and throat.

There have been reports that in rare cases, physicians may have mistakenly injected the drug into areas close to the esophagus, including other vital organs, resulting in serious health complications for the patient, including reduced kidney function, internal bleeding, and even death.

Despite extreme care by doctors to avoid such incidents, it is difficult to discern whether or not the liquid has been injected improperly.

Patients who have been given an inaccurate injection may experience the following symptoms:
·    Pain in the chest or side
·    Cough
·    Shortness of breath
·    Difficulty swallowing
·    Significant weight loss
·    Fever
·    “Flu-like” symptoms
·    Fainting
·    Weakness
·    Fatigue

Even when ENTERYX® is injected properly, it is still possible that long-term complications will occur.
In at least two of the reported cases, patients experienced some of the above symptoms up to a month and a half after their procedure and even though ENTERYX® was injected properly.

The FDA advised patients who have had the ENTERYX® procedure within the last seven weeks, to contact their physicians immediately in the event that they experience any of the above symptoms, even if they have already been treated in the emergency room.

Doctors may order a follow-up procedure to confirm or rule out improper injection of the ENTERYX® product.

FDA and Boston Scientific are working to make sure that physicians treating patients with ENTERYX® products are notified of the reported problems and receive accurate, up-to-date information. Additional information on this recall is available at http://www.fda.gov/cdrh/safety/101405-enteryx.html.